1 00:00:05,200 --> 00:00:08,800 MY NAME IS DAVID SHURTLEFF FOR 2 00:00:08,800 --> 00:00:10,120 THE NATIONAL CENTER FOR 3 00:00:10,120 --> 00:00:11,520 COMPLIMENTARY AND INTEGRATIVE 4 00:00:11,520 --> 00:00:13,200 HEALTH AND IT'S MY PLEASURE TO 5 00:00:13,200 --> 00:00:17,840 WELL CHILDRWELCOME EVERYONE ON 6 00:00:17,840 --> 00:00:19,760 INTEROCEPTION FUNCTIONAL 7 00:00:19,760 --> 00:00:20,080 NEUROCIRCUITS. 8 00:00:20,080 --> 00:00:22,440 THIS IS THE INAUGURAL AND ANNUAL 9 00:00:22,440 --> 00:00:24,080 INVESTIGATOR MEETING AND I MUST 10 00:00:24,080 --> 00:00:26,280 SAY IT'S A PLEASURE TO BE 11 00:00:26,280 --> 00:00:28,040 ACTUALLY HERE IN PERSON BEFORE A 12 00:00:28,040 --> 00:00:29,680 LIVE AUDIENCE SEEING EVERYBODY 13 00:00:29,680 --> 00:00:33,000 IN 3D RATHER THAN OUR TYPICAL 14 00:00:33,000 --> 00:00:33,920 HOLLYWOOD SQUARES. 15 00:00:33,920 --> 00:00:36,000 SO, INTEROCEPTION, THE PROCESS 16 00:00:36,000 --> 00:00:38,920 BY WHICH OUR BODY SENSES, 17 00:00:38,920 --> 00:00:40,120 INTERPRETS SIGNALS FROM WITHIN. 18 00:00:40,120 --> 00:00:44,720 AS THE DEPUTY DIRECTOR OF NCCIH, 19 00:00:44,720 --> 00:00:47,000 FOR THE PAST 10 YEARS NOW, I CAN 20 00:00:47,000 --> 00:00:49,120 SAY NCCIH HAS BEEN INTERESTED IN 21 00:00:49,120 --> 00:00:51,240 THE STUDY OF INTEROCEPTION 22 00:00:51,240 --> 00:00:53,360 PROCESSES AS RELATES TO SELF 23 00:00:53,360 --> 00:00:56,960 REGULATION, MAINTAINING 24 00:00:56,960 --> 00:00:58,280 HOMEOSTASIS AND MEDICATION CAN 25 00:00:58,280 --> 00:01:00,880 RESULT IN REFLECTION OF THESE 26 00:01:00,880 --> 00:01:02,400 INTER ACCEPTIVE PROCESSES AND 27 00:01:02,400 --> 00:01:04,560 PROMOTING ADAPTIVE BEHAVIOR AND 28 00:01:04,560 --> 00:01:05,400 WELLBEING. 29 00:01:05,400 --> 00:01:07,880 IT'S AN EXCITING AREA FOR NCCIH 30 00:01:07,880 --> 00:01:10,360 FOR SURE OVER THESE MANY YEARS, 31 00:01:10,360 --> 00:01:11,440 CERTAINLY, INTEROCEPTION 32 00:01:11,440 --> 00:01:13,000 PROCESSES AND DIS-REGULATED 33 00:01:13,000 --> 00:01:14,920 INTEROCEPTION PROCESSES IN 34 00:01:14,920 --> 00:01:17,680 PARTICULAR, ARE ASSOCIATED WITH 35 00:01:17,680 --> 00:01:18,200 MANY HEALTH CONDITIONS 36 00:01:18,200 --> 00:01:20,320 ININCLUDEDDING PAIN, AND ANXIETY 37 00:01:20,320 --> 00:01:23,640 DISORDERS, MOOD DISORDERS, PTSD, 38 00:01:23,640 --> 00:01:25,640 OBSESSIVE COMPULSIVE BEHAVIOR, 39 00:01:25,640 --> 00:01:27,040 AUTISM, EATING DISORDERS, 40 00:01:27,040 --> 00:01:29,280 ADDICTION AND SOMATIC SYMPTOM 41 00:01:29,280 --> 00:01:30,840 DISORDERS AND OF COURSE OTHERS. 42 00:01:30,840 --> 00:01:35,720 WHICH GO WELL BEYOND NCCIH PER 43 00:01:35,720 --> 00:01:39,320 HAVE YOU SPARKING CENTER ACROSS 44 00:01:39,320 --> 00:01:41,120 CENTERS AT THE NIH. 45 00:01:41,120 --> 00:01:46,040 IN ADDICTION ADDITION, THERE AE 46 00:01:46,040 --> 00:01:47,960 UNDERSTANDING THE BASIC 47 00:01:47,960 --> 00:01:48,960 MECHANISMS OF INTEROCEPTION THAT 48 00:01:48,960 --> 00:01:50,840 COULD LEAD TO IMPROVED DISEASE 49 00:01:50,840 --> 00:01:52,320 MODELS AND IMPROVE TREATMENT 50 00:01:52,320 --> 00:01:53,200 STRAT GOES FOR MANY OF THE 51 00:01:53,200 --> 00:01:56,520 HEALTH CONDITIONS THAT I JUST 52 00:01:56,520 --> 00:01:56,800 MENTIONED. 53 00:01:56,800 --> 00:01:58,040 IMPORTANTLY, THE NIH BLUE PRINT 54 00:01:58,040 --> 00:02:00,080 FOR NEUROSCIENCE RESEARCH 55 00:02:00,080 --> 00:02:02,000 COLLABORATIVE FRAMEWORK THAT 56 00:02:02,000 --> 00:02:03,040 INCLUDES 14 NIH INSTITUTES IN 57 00:02:03,040 --> 00:02:04,800 CENTERS AND OFFICES THAT SUPPORT 58 00:02:04,800 --> 00:02:06,960 RESEARCH ON THE NERVOUS SYSTEM, 59 00:02:06,960 --> 00:02:09,680 PROVIDES A GREAT OPPORTUNITY FOR 60 00:02:09,680 --> 00:02:11,120 LIKE-MINDED INSTITUTES IN 61 00:02:11,120 --> 00:02:12,520 CENTERS TO COME TOGETHER TO 62 00:02:12,520 --> 00:02:15,080 ADDRESS COMMON INTERESTS AND 63 00:02:15,080 --> 00:02:17,560 ADDRESS UNIQUE SCIENTIFIC 64 00:02:17,560 --> 00:02:18,360 CHALLENGES AND CERTAINLY 65 00:02:18,360 --> 00:02:19,920 INTEROCEPTION FALLS INTO THAT 66 00:02:19,920 --> 00:02:20,160 CATEGORY. 67 00:02:20,160 --> 00:02:21,680 JUST TO GIVE YOU A LITTLE 68 00:02:21,680 --> 00:02:23,160 BACKGROUND, THE BLUE PRINT WAS 69 00:02:23,160 --> 00:02:27,080 ESTABLISHED IN 2004 AND SOME 18 70 00:02:27,080 --> 00:02:29,600 YEARS AGO. 71 00:02:29,600 --> 00:02:31,600 AS THE FLAGSHIP PROGRAM TO BRING 72 00:02:31,600 --> 00:02:33,000 TOGETHER MANY BRAIN INSTITUTES 73 00:02:33,000 --> 00:02:35,840 ACROSS THE NIH TO ACCELERATE AND 74 00:02:35,840 --> 00:02:38,760 TRANSFORM DISCOVERIES OF THE 75 00:02:38,760 --> 00:02:40,560 BRAIN IN FUNCTION AND IN HEALTH 76 00:02:40,560 --> 00:02:42,560 AND AGING AND DISEASE. 77 00:02:42,560 --> 00:02:43,880 IN FACT, IT WAS A PRECURSOR TO 78 00:02:43,880 --> 00:02:46,480 THE BRAIN INITIATIVE HAVING THE 79 00:02:46,480 --> 00:02:47,880 BLUE PRINT HAVING CONTRIBUTED TO 80 00:02:47,880 --> 00:02:51,160 THE BRAIN INITIATIVE EARLY ON. 81 00:02:51,160 --> 00:02:52,760 WITH REGARD TO INTEROCEPTION IN 82 00:02:52,760 --> 00:02:55,080 2008, THE BLUE PRINT SPONSORED A 83 00:02:55,080 --> 00:02:57,000 WORKSHOP, THE SCIENCE OF 84 00:02:57,000 --> 00:02:58,280 INTERCEPTION IT'S ROLE IN 85 00:02:58,280 --> 00:03:00,600 NERVOUS SYSTEM DISORDERS AND 86 00:03:00,600 --> 00:03:05,840 CONDUCT A GRANT PORTFOLIO WITH 87 00:03:05,840 --> 00:03:07,120 FUNDED RESEARCH ON INTEROCEPTION 88 00:03:07,120 --> 00:03:08,040 ACROSS THE NIH. 89 00:03:08,040 --> 00:03:10,080 IT WAS QUITE CLEAR AND EVIDENCE 90 00:03:10,080 --> 00:03:11,480 THAT MORE BASIC RESEARCH WAS 91 00:03:11,480 --> 00:03:14,200 NEEDED IN THIS AREA SEEING THE 92 00:03:14,200 --> 00:03:16,920 NEED AND EXCITED ABOUT THE 93 00:03:16,920 --> 00:03:18,120 OPPORTUNITY, THE BLUE PRINT IN 94 00:03:18,120 --> 00:03:19,680 SEPTEMBER OF 2020 ASKED A 95 00:03:19,680 --> 00:03:21,320 REQUEST FOR APPLICATIONS TO 96 00:03:21,320 --> 00:03:23,320 SUPPORT THE STUDY OF FUNCTIONAL 97 00:03:23,320 --> 00:03:24,680 NERVE CIRCUITS OF INTEROCEPTION. 98 00:03:24,680 --> 00:03:26,560 THAT LED TO SUBMISSION OF 99 00:03:26,560 --> 00:03:27,840 FUNDING OF YOUR APPLICATIONS, 100 00:03:27,840 --> 00:03:30,920 THE PEOPLE IN THIS ROOM, WHICH 101 00:03:30,920 --> 00:03:38,480 BRINGS US HERE TODAY TO LEARN 102 00:03:38,480 --> 00:03:40,320 ABOUT THE GREAT WORK YOU'VE DONE 103 00:03:40,320 --> 00:03:42,400 AND WE'RE EXCITED TO HEAR ABOUT 104 00:03:42,400 --> 00:03:43,520 IT THE NEXT COUPLE OF DAYS. 105 00:03:43,520 --> 00:03:47,520 I WANT TO THANK YOU TO BE PART 106 00:03:47,520 --> 00:03:50,400 OF THIS FOCUSING ON DISSECT AND 107 00:03:50,400 --> 00:03:53,120 DETERMINING THE FUNCTION OF 108 00:03:53,120 --> 00:03:54,480 NEUROCIRCUITS THAT CONNECT 109 00:03:54,480 --> 00:03:56,320 ORGANS AND TISSUES WITH THE 110 00:03:56,320 --> 00:03:58,360 CENTRAL NERVOUS SYSTEM. 111 00:03:58,360 --> 00:03:59,920 CLEARLY IT'S AN IMPORTANT AREA 112 00:03:59,920 --> 00:04:02,240 FOR THE NEUROSCIENCE BLUE PRINT 113 00:04:02,240 --> 00:04:03,600 AND NIH AND WITH THAT I'LL TURN 114 00:04:03,600 --> 00:04:06,200 IT BACK OVER TO MY COLLEAGUE FOR 115 00:04:06,200 --> 00:04:07,120 THE NEXT STEPS. 116 00:04:07,120 --> 00:04:11,240 THANK YOU AGAIN FOR COMING. 117 00:04:11,240 --> 00:04:14,920 [APPLAUSE] 118 00:04:14,920 --> 00:04:17,720 >>THANK YOU SO MUCH, DAVID AND 119 00:04:17,720 --> 00:04:20,760 I WOULD LIKE NEXT TO INTRODUCE 120 00:04:20,760 --> 00:04:23,360 Dr. WEN CHEN, THE BRANCH CHIEF 121 00:04:23,360 --> 00:04:25,160 FROM THE DIVISION OF EXTRAMURAL 122 00:04:25,160 --> 00:04:26,840 RESEARCH AT NCCIH AND SHE'S 123 00:04:26,840 --> 00:04:29,560 GOING TO TALK TO US TODAY ABOUT 124 00:04:29,560 --> 00:04:32,920 AN OVERVIEW AND UPDATE OF THE 125 00:04:32,920 --> 00:04:34,360 NIH INTEROCEPTION PROGRAM. 126 00:04:34,360 --> 00:04:35,480 >>THANK YOU Dr. SHURTLEFF 127 00:04:35,480 --> 00:04:37,640 FOR YOUR INTRODUCTION. 128 00:04:37,640 --> 00:04:40,160 WELCOME TO THE FIRST NIH 129 00:04:40,160 --> 00:04:41,720 INVESTIGATOR MEETING ON 130 00:04:41,720 --> 00:04:46,720 FUNCTIONAL NEUROCIRCUITS OF 131 00:04:46,720 --> 00:04:47,160 INTEROCEPTION. 132 00:04:47,160 --> 00:04:51,520 TODAY, I WILL PROVIDE SOME 133 00:04:51,520 --> 00:04:54,680 UPDATES ON THE WORKING GROUP AND 134 00:04:54,680 --> 00:04:58,520 THE HISTORY OF THE NIH 135 00:04:58,520 --> 00:05:00,560 BLUEPRINTS FOR NEUROSCIENCE 136 00:05:00,560 --> 00:05:06,800 RESEARCH INTEROCEPTION 137 00:05:06,800 --> 00:05:07,640 INITIATIVE. 138 00:05:07,640 --> 00:05:08,680 FUNDING OPPORTUNITIES WITH 139 00:05:08,680 --> 00:05:09,920 ACKNOWLEDGMENT OF ANNUAL 140 00:05:09,920 --> 00:05:12,760 INVESTIGATOR MEETINGS PLANNING 141 00:05:12,760 --> 00:05:13,040 COMMITTEE. 142 00:05:13,040 --> 00:05:15,960 SO THERE'S BEEN A STRONG AND 143 00:05:15,960 --> 00:05:18,200 BROAD INTEREST IN SUPPORT WITHIN 144 00:05:18,200 --> 00:05:20,440 THE NATIONAL INSTITUTE FOR 145 00:05:20,440 --> 00:05:22,560 HEALTH AND OUR TRANS NIH 146 00:05:22,560 --> 00:05:23,880 INTEROCEPTION RESEARCH WORKING 147 00:05:23,880 --> 00:05:26,560 GROUP CONSISTS OF PROGRAM 148 00:05:26,560 --> 00:05:28,960 OFFICIALS AND SCIENTIFIC REVIEW 149 00:05:28,960 --> 00:05:31,440 OFFICERS ACROSS 15 NIH 150 00:05:31,440 --> 00:05:33,360 INSTITUTES CENTERS AND OFFICES. 151 00:05:33,360 --> 00:05:35,520 AND WE IMMEDIATE LEAST QUARTERLY 152 00:05:35,520 --> 00:05:37,160 TO DISCUSS AND COORDINATE 153 00:05:37,160 --> 00:05:44,360 TRANSPORTATION RELATED RESEARCH 154 00:05:44,360 --> 00:05:45,680 INITIATIVES AND ACTIVITIES. 155 00:05:45,680 --> 00:05:47,320 THE START MEMBERS HERE ARE THE 156 00:05:47,320 --> 00:05:50,320 PROGRAM OFFICIALS WHO ORIGINALLY 157 00:05:50,320 --> 00:05:52,200 WORKED TOGETHER TO KICKOFF THE 158 00:05:52,200 --> 00:05:55,160 CONCEPT OF INTEROCEPTION WITHIN 159 00:05:55,160 --> 00:05:55,760 THE NIH. 160 00:05:55,760 --> 00:05:58,800 SOME OF YOU MAY BE FAMILIAR WITH 161 00:05:58,800 --> 00:06:01,360 AT LEAST TWO ON GOING LARGE 162 00:06:01,360 --> 00:06:02,880 INITIATIVES WITHIN THE NIH ONE 163 00:06:02,880 --> 00:06:05,360 IS CALLED THE SPARK AND IT 164 00:06:05,360 --> 00:06:07,400 STANDS FOR STIMULATING 165 00:06:07,400 --> 00:06:10,360 PERIPHERAL ACTIVITIES TO RELIEF 166 00:06:10,360 --> 00:06:12,800 CONDITIONS AND IT'S A 10-YEAR 167 00:06:12,800 --> 00:06:14,840 COMMON FUND INITIATIVE WHICH 168 00:06:14,840 --> 00:06:17,320 FOCUSED ON NEURO STIMULATION OF 169 00:06:17,320 --> 00:06:21,640 THE PERIPHERAL ORGANS. 170 00:06:21,640 --> 00:06:27,040 AND THE BRAIN INITIATIVE, THAT'S 171 00:06:27,040 --> 00:06:28,840 AIMING AT REVOLUTIONARY OUR 172 00:06:28,840 --> 00:06:31,360 UNDERSTANDING OF THE HUMAN 173 00:06:31,360 --> 00:06:33,680 BRAIN. 174 00:06:33,680 --> 00:06:36,440 IN 2018, WITH THE SUPPORT OF THE 175 00:06:36,440 --> 00:06:38,040 NIH BLUEPRINTS FOR NEUROSCIENCE 176 00:06:38,040 --> 00:06:41,400 RESEARCH WE LAUNCHED A NEW BLUE 177 00:06:41,400 --> 00:06:48,760 PRINT INITIATIVE CALLED 178 00:06:48,760 --> 00:06:50,200 INTEROCEPTION, AIMING TO CONNECT 179 00:06:50,200 --> 00:06:52,800 THE BRAIN AND BODY AND FILL THE 180 00:06:52,800 --> 00:06:56,120 KNOWLEDGE GAPS BETWEEN SPARC AND 181 00:06:56,120 --> 00:06:59,040 BRAIN INITIATIVE. 182 00:06:59,040 --> 00:07:00,640 AS Dr. SHURTLEFF MENTIONED 183 00:07:00,640 --> 00:07:01,720 EARLIER, WE KICKED OFF THAT 184 00:07:01,720 --> 00:07:05,400 EFFORT WITH A TWO-DAY WORKSHOP 185 00:07:05,400 --> 00:07:07,400 IN 2019 AND THE WORKSHOP 186 00:07:07,400 --> 00:07:10,400 FEATURED TWO KEYNOTE SPEAKERS 187 00:07:10,400 --> 00:07:12,360 WHO MANY OF US HAVE FAMILIAR 188 00:07:12,360 --> 00:07:22,280 WITH NOW AND WHO PROVIDED A LOOL 189 00:07:22,280 --> 00:07:26,000 AND Dr. HUGO WHO GAVE US A 190 00:07:26,000 --> 00:07:28,840 REVIEW ON THE NERVOUS SYSTEM 191 00:07:28,840 --> 00:07:30,720 DISORDERS THAT ARE IMPACTED BY 192 00:07:30,720 --> 00:07:31,320 DYSFUNCTIONS OF THE 193 00:07:31,320 --> 00:07:32,320 INTEROCEPTION PROCESSES AND 194 00:07:32,320 --> 00:07:46,680 PERIPHERAL ORGANS. 195 00:07:46,680 --> 00:07:48,960 WE DECIDED TO HAVE 196 00:07:48,960 --> 00:07:50,880 A PROGRESS OF REGULATING. 197 00:07:50,880 --> 00:07:59,520 WE PUBLISHED A RFA AS Dr. 198 00:07:59,520 --> 00:08:03,480 SHURTLEFF MENTIONED EARLIER AND 199 00:08:03,480 --> 00:08:05,240 WITHIN THE BLUE PRINT WE DECIDED 200 00:08:05,240 --> 00:08:06,920 TO FOCUS ON THE MAPPING, 201 00:08:06,920 --> 00:08:08,800 FUNCTIONAL MAPPING OF THE 202 00:08:08,800 --> 00:08:11,720 CONNECTIONS BETWEEN THE 203 00:08:11,720 --> 00:08:12,360 PERIPHERAL ORGANS AND THE BRAIN 204 00:08:12,360 --> 00:08:14,040 AS OUR VERY FIRST STEP TO 205 00:08:14,040 --> 00:08:18,280 SUPPORT RESEARCH ON 206 00:08:18,280 --> 00:08:18,720 INTEROCEPTION. 207 00:08:18,720 --> 00:08:23,760 FOR THAT RFA, WE BASICALLY LAID 208 00:08:23,760 --> 00:08:26,840 OUT THE NEURO PATHWAYS THAT 209 00:08:26,840 --> 00:08:29,480 WE'RE HOPING THE SCIENTIFIC 210 00:08:29,480 --> 00:08:31,360 COMMUNITY WILL BE ABLE TO MAP 211 00:08:31,360 --> 00:08:33,480 OUT AND THAT INCLUDES THE 212 00:08:33,480 --> 00:08:35,240 ASCENDING NEURO PATHWAYS AND 213 00:08:35,240 --> 00:08:39,440 ACTUALLY THIS IS PROBABLY A GOOD 214 00:08:39,440 --> 00:08:44,640 WAY TO -- IT'S NOT SENSING 215 00:08:44,640 --> 00:08:47,160 ANYTHING. 216 00:08:47,160 --> 00:08:48,440 BASICALLY WE WILL MAP NEURO 217 00:08:48,440 --> 00:08:50,000 PATHWAYS ARE COMING FROM THE 218 00:08:50,000 --> 00:08:51,640 PERIPHERAL ORGANS THAT GO 219 00:08:51,640 --> 00:08:55,040 THROUGH EITHER THE VAGAL NERVES 220 00:08:55,040 --> 00:08:56,560 AND GET INTO THE BRAIN OR GO 221 00:08:56,560 --> 00:08:58,440 THROUGH THE DORRAL GANGLIA AND 222 00:08:58,440 --> 00:09:00,320 THE SPINAL PATHWAY TO GET INTO 223 00:09:00,320 --> 00:09:02,200 THE BRAIN AND WITHIN THE BRAIN, 224 00:09:02,200 --> 00:09:04,960 WE WILL LIKE TO HAVE A MORE 225 00:09:04,960 --> 00:09:06,640 IN-DEPTH UNDERSTANDING ABOUT THE 226 00:09:06,640 --> 00:09:09,400 CIRCUS INVOLVED IN THE BRAIN OF 227 00:09:09,400 --> 00:09:11,440 SENSING AND MOSTLY INTERPRETING 228 00:09:11,440 --> 00:09:13,000 INTEGRATING THOSE INTERNAL 229 00:09:13,000 --> 00:09:14,280 SIGNALS AND AS WELL AS THE 230 00:09:14,280 --> 00:09:16,640 ACTUALLY GENERATING POTENTIALLY 231 00:09:16,640 --> 00:09:18,360 REGULATING SIGNALS THAT WILL 232 00:09:18,360 --> 00:09:20,640 THEN COME BACKOUT OF THE BRAIN 233 00:09:20,640 --> 00:09:22,400 SO EITHER THE VAGAL PATHWAY OR 234 00:09:22,400 --> 00:09:27,480 THE SPINAL PATHWAY AND TO 235 00:09:27,480 --> 00:09:29,080 REGULATE THE INTERNAL SIGNALS OF 236 00:09:29,080 --> 00:09:30,240 THE PERIPHERAL. 237 00:09:30,240 --> 00:09:31,360 THOSE ARE THE SCOPE OF THE 238 00:09:31,360 --> 00:09:36,520 PARTICULAR RFA THAT WE PUBLISHED 239 00:09:36,520 --> 00:09:39,120 AND THAT RFA, I'M PLEASED TO SAY 240 00:09:39,120 --> 00:09:42,520 THE RFA HAD ATTRACTED VERY LONG 241 00:09:42,520 --> 00:09:46,360 PROPOSALS ACROSS THE SCIENTIFIC 242 00:09:46,360 --> 00:09:47,800 COMMUNITY AND THE BLUE PRINT 243 00:09:47,800 --> 00:09:50,000 INITIATIVE WAS ABLE TO SUPPORT 244 00:09:50,000 --> 00:09:53,200 SEVEN OF THE AWARDS. 245 00:09:53,200 --> 00:09:54,680 IF MY SLIDES WOULD SHOW YOU 246 00:09:54,680 --> 00:09:57,440 WOULD BE ABLE TO SEE A NICE 247 00:09:57,440 --> 00:09:58,680 DISTRIBUTION OF THOSE SEVEN 248 00:09:58,680 --> 00:10:01,280 AWARDS AND ALL OF THE AWARDEES 249 00:10:01,280 --> 00:10:04,920 ARE HERE TODAY AND WE WILL BE 250 00:10:04,920 --> 00:10:08,120 HEARING THEIR INITIAL EFFORTS 251 00:10:08,120 --> 00:10:10,960 FUNDED BY THIS INITIATIVE. 252 00:10:10,960 --> 00:10:21,800 SO WITHIN THIS AMONG OF SEVEN FN 253 00:10:36,360 --> 00:10:39,400 AWARDS WILL STUDY VAGAL PATHWAYS 254 00:10:39,400 --> 00:10:42,520 AND THREE OF THEM STUDY SPINAL 255 00:10:42,520 --> 00:10:43,920 PATHWAYS AND WITHIN THE BRAIN, 256 00:10:43,920 --> 00:10:46,520 THE SEVEN AWARDS WILL 257 00:10:46,520 --> 00:10:49,760 COLLECTIVELY TEST ALL THE 258 00:10:49,760 --> 00:10:52,400 HYPOTHESIZED BRAIN AREAS 259 00:10:52,400 --> 00:10:54,560 INVOLVED ON HUMAN IMAGING 260 00:10:54,560 --> 00:10:58,040 STUDIES AND SOME OF THEM WILL GO 261 00:10:58,040 --> 00:10:58,960 EVEN BEYOND TO TEST SOME OF THE 262 00:10:58,960 --> 00:11:01,000 BRAIN AREAS THAT HAVE NOT BEEN 263 00:11:01,000 --> 00:11:02,760 KNOWN, MAYBE INVOLVED IN 264 00:11:02,760 --> 00:11:04,040 INTEROCEPTION AND YOU MAY HEAR 265 00:11:04,040 --> 00:11:07,400 ABOUT SOME OF THOSE WORK TODAY. 266 00:11:07,400 --> 00:11:10,800 AS THE BLUE PRINT RFA FOCUSED 267 00:11:10,800 --> 00:11:12,200 MORE ON THE BASIC PHYSICAL 268 00:11:12,200 --> 00:11:15,800 OWOLOGY OF PHYSIOLOGICAL PROCESS 269 00:11:15,800 --> 00:11:17,320 OF INTEROCEPTION WE ALSO FOLLOW 270 00:11:17,320 --> 00:11:21,800 THE PUBLICATION OF RFA WITH A 271 00:11:21,800 --> 00:11:23,560 MULTI-IC FUNDING OPPORTUNITY 272 00:11:23,560 --> 00:11:25,800 ANNOUNCEMENT IN THE FORM OF 273 00:11:25,800 --> 00:11:33,680 NOTICE OF SPECIAL INTEREST 274 00:11:33,680 --> 00:11:37,200 ISSUED BY 10 OFFICES INCLUDING 275 00:11:37,200 --> 00:11:38,640 NCCH, NATIONAL INSTITUTE OF 276 00:11:38,640 --> 00:11:41,480 AGING, DENTAL AND CRANIAL 277 00:11:41,480 --> 00:11:44,280 RESEARCH, DRUG ABUSE, 278 00:11:44,280 --> 00:11:46,080 ENVIRONMENTAL HEALTH AND 279 00:11:46,080 --> 00:11:49,200 SCIENCES AND AT NIHS AND MENTAL 280 00:11:49,200 --> 00:11:55,880 HEALTH AND CANCER INSTITUTE, AND 281 00:11:55,880 --> 00:11:59,720 NATIONAL HEART LUNG AND SOCIAL 282 00:11:59,720 --> 00:12:06,640 SCIENCES RESEARCH ON WOMEN'S 283 00:12:06,640 --> 00:12:07,040 HEALTH. 284 00:12:07,040 --> 00:12:14,120 THIS WILL LAST AT LEAST THROUGH 285 00:12:14,120 --> 00:12:24,520 2024 AND RELEVANT TO THE 286 00:12:34,440 --> 00:12:35,840 PARTICIPATING INSTITUTES AT NIH 287 00:12:35,840 --> 00:12:38,840 AND I ENCOURAGE YOU THINK ABOUT 288 00:12:38,840 --> 00:12:40,040 SUBMITTING THE APPLICATION 289 00:12:40,040 --> 00:12:42,080 THROUGH THE NOTICE AND REACH OUT 290 00:12:42,080 --> 00:12:43,640 TO THE SPECIFIC OFFICERS LISTED 291 00:12:43,640 --> 00:12:52,320 IN THE ANNOUNCEMENT. 292 00:12:52,320 --> 00:12:56,080 >>WE'RE GOING TO END UPTAKING 293 00:12:56,080 --> 00:12:56,960 ANOTHER QUICK PAUSE AND WE'RE 294 00:12:56,960 --> 00:12:59,280 GOING TO ACTUALLY SWITCH TO A 295 00:12:59,280 --> 00:13:01,760 ZOOM MEETING AND THAT IS GOING 296 00:13:01,760 --> 00:13:03,560 TO BE LIVE CASTED AS WELL SO THE 297 00:13:03,560 --> 00:13:04,920 PEOPLE THAT ARE ON-LINE JUST 298 00:13:04,920 --> 00:13:07,200 STAY TUNED AND THAT WILL GET 299 00:13:07,200 --> 00:14:27,520 SWITCHED OVER. 300 00:14:27,520 --> 00:14:31,320 >>OF COURSE, AGAIN, WE HAVE AN 301 00:14:31,320 --> 00:14:32,720 ABUNDANCE OF OPTIONS AVAILABLE 302 00:14:32,720 --> 00:14:33,640 TO US. 303 00:14:33,640 --> 00:14:35,400 WE CAN GO ELECTRICAL STIMULATION 304 00:14:35,400 --> 00:14:38,560 THAT USED IN CLINICS FOR DBS FOR 305 00:14:38,560 --> 00:14:41,480 INSTANCE AND THERE WE HAVE TO 306 00:14:41,480 --> 00:14:44,120 PRECISION BUT WE LACK THE CELL 307 00:14:44,120 --> 00:14:46,040 TYPES SPECIFICITY AND IF WE NEED 308 00:14:46,040 --> 00:14:49,920 THAT WE CAN TURN TO CONTROLLING 309 00:14:49,920 --> 00:14:51,680 SPECIFIC CELLS WITH LIGHT 310 00:14:51,680 --> 00:14:55,120 HOWEVER IT REQUIRES GENETIC 311 00:14:55,120 --> 00:14:57,440 HARDWARE AND WE CAN TURN TO 312 00:14:57,440 --> 00:14:59,080 PHARMACOLOGY TO GET ACCESS TO 313 00:14:59,080 --> 00:15:01,760 SPECIFIC RECEPTORS AND THERE WE 314 00:15:01,760 --> 00:15:03,960 MAY NOT HAVE ACCESS TO SPECIFIC 315 00:15:03,960 --> 00:15:06,640 CELLS AND WE ALSO MAY HAVE 316 00:15:06,640 --> 00:15:09,120 LIMITED PRECISION UNLESS WE 317 00:15:09,120 --> 00:15:11,920 RESORT TO INVASIVE DEVICES THAT 318 00:15:11,920 --> 00:15:13,880 MAYELING CHALLENGING. 319 00:15:13,880 --> 00:15:20,040 WE HAVE VERSION OF PHARMACOLOGY 320 00:15:20,040 --> 00:15:23,240 ENDOWING US STRUGGLING WITH THE 321 00:15:23,240 --> 00:15:29,720 FAPHARMACOLOGY. 322 00:15:29,720 --> 00:15:34,280 SO IF WE ARE THINKING ABOUT THE 323 00:15:34,280 --> 00:15:37,600 SIMULTANEOUS RECORDINGS WE NEED 324 00:15:37,600 --> 00:15:40,080 TO THINK OF INTEGRATION OF ALL 325 00:15:40,080 --> 00:15:44,960 THE DIFFERENT MODALITY AND OUR 326 00:15:44,960 --> 00:15:48,440 DEVICES ARE BULKY AND DIFFERENT 327 00:15:48,440 --> 00:15:50,080 DESIGN CRITERIA NOT MET FOR 328 00:15:50,080 --> 00:15:52,160 DIFFERENT TECHNOLOGY BUT ALSO, 329 00:15:52,160 --> 00:15:54,120 THE ABILITY TO INTERFACE WITH 330 00:15:54,120 --> 00:15:56,440 ORGANS WITHOUT DAMAGING THEM 331 00:15:56,440 --> 00:16:00,840 DIMINISHES AND BECAUSE ALREADY 332 00:16:00,840 --> 00:16:04,000 THEY ARE STRUGGLING A MISMATCH 333 00:16:04,000 --> 00:16:05,760 WITHIN THE TISSUE THAT WE'RE 334 00:16:05,760 --> 00:16:07,440 TRYING TO RECORD FROM OR 335 00:16:07,440 --> 00:16:08,720 MODULATE AND THE DEVICE 336 00:16:08,720 --> 00:16:10,600 AVAILABLE TO US SO HOW DO WE 337 00:16:10,600 --> 00:16:12,280 SOLVE THOSE TWO CHALLENGES 338 00:16:12,280 --> 00:16:13,960 SIMULTANEOUSLY AND COMBINE TOOLS 339 00:16:13,960 --> 00:16:15,560 FOR RECORDING AND MODULATION IN 340 00:16:15,560 --> 00:16:17,720 THE CONTEXT OF BRAIN ORGAN 341 00:16:17,720 --> 00:16:18,000 CIRCUITS? 342 00:16:18,000 --> 00:16:20,280 IN OUR GROUP, WE BORROW FROM 343 00:16:20,280 --> 00:16:22,040 TELE COMMUNICATIONS AND WE 344 00:16:22,040 --> 00:16:25,360 DESIGN FIBER-BASED DEVICES 345 00:16:25,360 --> 00:16:26,480 CAPABLE OF SIMULTANEOUS 346 00:16:26,480 --> 00:16:27,720 INTERROGATION AND RECORDING OF 347 00:16:27,720 --> 00:16:30,760 NEURAL ACTIVITY AND THE WAY 348 00:16:30,760 --> 00:16:32,920 FIBER WORKS, IT STARTS WITH THE 349 00:16:32,920 --> 00:16:37,760 MAMACRO SCALE MODEL AND INTO THT 350 00:16:37,760 --> 00:16:41,280 MACRO SCALE MODEL WE CAN 351 00:16:41,280 --> 00:16:42,920 INCORPORATE ALL THE DESIRED 352 00:16:42,920 --> 00:16:46,800 FEATURES, A POLYMER AND MICRO 353 00:16:46,800 --> 00:16:50,440 FLUID FOR DRUG DELIVERY AND 354 00:16:50,440 --> 00:16:51,080 ELECTRICAL CONDUCTIVE CHANNELS 355 00:16:51,080 --> 00:16:52,840 FOR RECORDING AND TAKE THAT 356 00:16:52,840 --> 00:16:56,840 STRUCTURE THAT IS IN THE MACRO 357 00:16:56,840 --> 00:16:57,840 SCALE WITH THE NUMBER OF 358 00:16:57,840 --> 00:16:59,080 CENTIMETERS OR INCHES AND HEAT 359 00:16:59,080 --> 00:17:00,760 IT AND PULL IT DOWN AND THE 360 00:17:00,760 --> 00:17:05,280 FEATURES TA STARTED OUT AS 361 00:17:05,280 --> 00:17:07,920 CENTIMETERS BECOME MYCRONS SO 362 00:17:07,920 --> 00:17:11,640 NOW WE HAVE A DEVICE AND CAN DO 363 00:17:11,640 --> 00:17:14,160 UP DRUG DELIVERY RECORDING AND 364 00:17:14,160 --> 00:17:18,040 WE CAN APPLY TO SIMULTANEOUS' 365 00:17:18,040 --> 00:17:19,920 DELIVERED GENES AND ENDOW 366 00:17:19,920 --> 00:17:21,920 OURSELVES WITH ON STICKAL 367 00:17:21,920 --> 00:17:23,560 SENSITIVITY AND MONITOR WHEN THE 368 00:17:23,560 --> 00:17:24,960 OPTICAL SENSITIVITY IS 369 00:17:24,960 --> 00:17:28,600 SUFFICIENT FOR US TO MANIPULATE 370 00:17:28,600 --> 00:17:30,280 BEHAVIOR SUCH AS IN THIS 371 00:17:30,280 --> 00:17:32,040 EXPERIMENT WHERE WE SEE OPTICAL 372 00:17:32,040 --> 00:17:34,200 CONTROL OF NEURAL ACTIVITY 373 00:17:34,200 --> 00:17:36,080 BECAUSE POSSIBLE 11 DAYS AND 374 00:17:36,080 --> 00:17:37,600 THEN IT BECOMES MORE AND MORE 375 00:17:37,600 --> 00:17:39,960 ROBUST AS THE TIME GOES ON. 376 00:17:39,960 --> 00:17:42,600 AND AS WE LEARN WHEN TO START 377 00:17:42,600 --> 00:17:48,240 OUR BEHAVIOR BEHAVIORAL EXPERIE 378 00:17:48,240 --> 00:17:50,640 CAN PROVIDE IT IN THE BRAIN AND 379 00:17:50,640 --> 00:17:52,760 START UNDERSTANDING NOT ONLY 380 00:17:52,760 --> 00:17:55,200 INDIVIDUAL REGIONS AND CELL 381 00:17:55,200 --> 00:17:56,240 TYPES BUT CIRCUITS. 382 00:17:56,240 --> 00:18:01,240 IF YOU LOOK AT AN EXAMPLE OF THE 383 00:18:01,240 --> 00:18:02,960 PROJECTION BETWEEN HIPPOCAMPUS 384 00:18:02,960 --> 00:18:05,840 AND BLA IMPLICATED IN ANNE 385 00:18:05,840 --> 00:18:07,680 SIGHLY LIKE PATTERNS IN RODENTS, 386 00:18:07,680 --> 00:18:09,880 WE CAN APPLY OUR DEVICES TO 387 00:18:09,880 --> 00:18:11,480 MODULATE THIS PROJECTION IN A RA 388 00:18:11,480 --> 00:18:17,800 VI TVARIETY OF WAYS IN AN OPEN D 389 00:18:17,800 --> 00:18:18,000 TEST. 390 00:18:18,000 --> 00:18:20,560 YOU CAN SEE AS A CONFIDENT MOUSE 391 00:18:20,560 --> 00:18:23,080 EXPLORES THE CORNERS BUT THE 392 00:18:23,080 --> 00:18:24,160 CENTER OF THE OPEN FIELD. 393 00:18:24,160 --> 00:18:28,000 WHEN WE STIMULATE THE EXCITED 394 00:18:28,000 --> 00:18:30,800 TERMINALS FROM AMYGDALA OUR 395 00:18:30,800 --> 00:18:32,800 ANIMAL IS MORE ANXIOUS AND 396 00:18:32,800 --> 00:18:35,440 STARTS STICKING TO THE CORNERS 397 00:18:35,440 --> 00:18:37,640 BUT NOW, THIS EFFECT IS QUITE 398 00:18:37,640 --> 00:18:39,120 ROBUST, BUT NOW WE CAN ACTUAL 399 00:18:39,120 --> 00:18:41,000 LOW USE OTHER FEATURES OF OUR 400 00:18:41,000 --> 00:18:45,520 DEVICE SUCH AS MICRO FLUIDICS 401 00:18:45,520 --> 00:18:50,920 AND WE CAN INJECT A BLOCKER CNQX 402 00:18:50,920 --> 00:18:53,960 AND COUPLE IT AND ABOLISH THE 403 00:18:53,960 --> 00:18:56,240 EFFECT OF STIMULATION DURING 404 00:18:56,240 --> 00:18:57,920 BEHAVIOR AND SHOWING US HOW WE 405 00:18:57,920 --> 00:19:01,400 CAN APPLY ALL OF THESE 406 00:19:01,400 --> 00:19:02,840 MODALITIES AND OF COURSE, THIS 407 00:19:02,840 --> 00:19:04,280 DEVOICE IS I HAVE SHOWN YOU ARE 408 00:19:04,280 --> 00:19:07,320 BASED ON POLYMER AND POLYMERS 409 00:19:07,320 --> 00:19:11,720 STILL HAVE GIG A PASCALS RATHER 410 00:19:11,720 --> 00:19:14,280 THAN THE ORGAN TISSUE THAT 411 00:19:14,280 --> 00:19:16,240 ACTUALLY HAVE MECHANICS OF 412 00:19:16,240 --> 00:19:21,560 JELL-O SO HOW CAN WE MAKE OUR 413 00:19:21,560 --> 00:19:24,120 DEVICES SO SENSE THEY WILL BEND 414 00:19:24,120 --> 00:19:25,600 EVEN WHEN THEY TOUCH JELL-O BUT 415 00:19:25,600 --> 00:19:26,960 AT THE SAME TIME FUNCTIONAL. 416 00:19:26,960 --> 00:19:28,880 WELL, LET'S MAKE THEM REALLY 417 00:19:28,880 --> 00:19:33,000 SMALL AND INCORPORATE THEM INTO 418 00:19:33,000 --> 00:19:36,760 ACTUAL JELL-O SUCH AS HYDRO GELS 419 00:19:36,760 --> 00:19:37,440 SHOWN HERE. 420 00:19:37,440 --> 00:19:38,400 HOW DOES IT WORK? 421 00:19:38,400 --> 00:19:40,440 WE TAKE A TINY STRUCTURE ALL OF 422 00:19:40,440 --> 00:19:42,480 WHICH CAPABLE OF RECORDINGS 423 00:19:42,480 --> 00:19:43,840 STIMULATION DRUG DELIVER ROW AND 424 00:19:43,840 --> 00:19:46,200 PUT THEM TOGETHER INTO ONE 425 00:19:46,200 --> 00:19:49,120 STRUCTURE AND IMBED THEM INTO A 426 00:19:49,120 --> 00:19:51,160 HIGHDRO GEL AND WE HAVE A DEVICE 427 00:19:51,160 --> 00:19:54,000 AS THIN AS YOUR HAIR AND 428 00:19:54,000 --> 00:19:59,120 MECHANICS OF A WET GOOD NOODLE. 429 00:19:59,120 --> 00:20:01,000 WE LEARN FROM THE WORLD OF ART 430 00:20:01,000 --> 00:20:03,920 AND THINK THE PAINT BRUSH 431 00:20:03,920 --> 00:20:14,360 INDIVIDUAL BRISTLE ARE -- 432 00:21:08,000 --> 00:21:10,240 >>SO HOW IS IT HELPING US IN 433 00:21:10,240 --> 00:21:13,000 OUR JOURNEY TO UNDERSTANDING 434 00:21:13,000 --> 00:21:13,720 INTEROCEPTION. 435 00:21:13,720 --> 00:21:23,840 HOW DO 436 00:21:47,000 --> 00:21:49,400 >>SO, IF THE VIDEO ACTUALLY 437 00:21:49,400 --> 00:21:50,840 PLAYED, WHICH YOU WOULD OBSERVE, 438 00:21:50,840 --> 00:21:53,680 IS THAT THE GUT NOT ONLY IS VERY 439 00:21:53,680 --> 00:21:56,400 THIN STRUCTURE, THAT HAS WALL 440 00:21:56,400 --> 00:22:02,840 THICKNESS OF ABOUT 300 MYCRONS 441 00:22:02,840 --> 00:22:13,360 IT'S UNDER A CONTINUOUS MOTION. 442 00:22:33,040 --> 00:22:36,120 >>USE THEIR SOFT MECHANICS TO 443 00:22:36,120 --> 00:22:39,680 ENABLE INTER FACES DIRECTLY INTO 444 00:22:39,680 --> 00:22:40,840 THE SPACE. 445 00:22:40,840 --> 00:22:42,680 WE CAN ASK OURSELVES IF WE'RE 446 00:22:42,680 --> 00:22:47,320 ABLE TO MODULATE CELLS WITHIN 447 00:22:47,320 --> 00:22:47,960 THE GUT WOULD THAT INFLUENCE 448 00:22:47,960 --> 00:22:51,360 THIS ANIMALS BEHAVIOR IN THE 449 00:22:51,360 --> 00:22:53,600 CONTEXT FIRST OF SOME BEHAVIORS 450 00:22:53,600 --> 00:22:55,320 THAT ARE PARTICULARLY LINKED TO 451 00:22:55,320 --> 00:22:57,120 THE GUT SUCH AS PREFERENCE FOR 452 00:22:57,120 --> 00:22:57,600 NUTRIENTS. 453 00:22:57,600 --> 00:23:01,960 AND FOR THIS WORK, WE 454 00:23:01,960 --> 00:23:12,280 COLLABORATED THIS 455 00:23:24,440 --> 00:23:26,600 SO WE THOUGHT CAN WE TEST THOSE 456 00:23:26,600 --> 00:23:28,400 HYPOTHESIS IN THE CONTEXT OF OUR 457 00:23:28,400 --> 00:23:30,520 ACTUAL BEHAVING ANIMAL BECAUSE 458 00:23:30,520 --> 00:23:34,000 IT WAS ONLY POSSIBLE IN VITRO. 459 00:23:34,000 --> 00:23:37,280 WORKING TOGETHER WITH DIEGO, WE 460 00:23:37,280 --> 00:23:42,520 ASKED WHETHER THOSE ENDOCRINE 461 00:23:42,520 --> 00:23:44,840 FOR SUGAR IN BEHAVING ANIMALS. 462 00:23:44,840 --> 00:23:50,040 MICE VERY QUICKLY LEARN THAT 463 00:23:50,040 --> 00:23:55,000 IT'S MORE VALUABLE THAN 464 00:23:55,000 --> 00:23:58,720 SUCRALOSE AND IF HE THEY INHIBIT 465 00:23:58,720 --> 00:24:08,480 THE CELLS AND IT'S DONE IN A 466 00:24:08,480 --> 00:24:09,560 AWAKE, MOVING ANIMALS. 467 00:24:09,560 --> 00:24:11,440 LET'S PUT THIS ALL TOGETHER. 468 00:24:11,440 --> 00:24:14,440 CAN WE USE THOSE TYPES OF PROBES 469 00:24:14,440 --> 00:24:17,080 AS I HAVE SHOWN YOU IN THE BRAIN 470 00:24:17,080 --> 00:24:18,840 AND THE GUT TO INTERFACE WITH 471 00:24:18,840 --> 00:24:21,880 BOTH OF THOSE SYSTEMS 472 00:24:21,880 --> 00:24:22,520 SIMULTANEOUSLY. 473 00:24:22,520 --> 00:24:27,960 CAN WE INTERFACE WITH THE BRAIN 474 00:24:27,960 --> 00:24:29,160 TO RECORD WHAT HAPPENS IN THE 475 00:24:29,160 --> 00:24:31,640 GUT AND VICE VERSA AND THEY'RE 476 00:24:31,640 --> 00:24:33,920 MAKING INITIAL STEPS AND WE'RE 477 00:24:33,920 --> 00:24:34,760 INTEGRATING SOPHISTICATED SOLID 478 00:24:34,760 --> 00:24:36,680 STATE ELECTRONICS INTO OUR 479 00:24:36,680 --> 00:24:39,120 FIBERS SO THAT WE CAN MANIPULATE 480 00:24:39,120 --> 00:24:41,040 THEM WIRELESSLY AT THE DISTANCE 481 00:24:41,040 --> 00:24:43,040 USING A SIMPLE COMPUTER 482 00:24:43,040 --> 00:24:44,320 INTERFACE AND HERE YOU ARE 483 00:24:44,320 --> 00:24:46,000 SEEING MANIPULATE OF DIFFERENT 484 00:24:46,000 --> 00:24:49,160 COLOR LEDs AS WELL AS DRUG 485 00:24:49,160 --> 00:24:50,680 INJECTIONS AND IF THIS VIDEO 486 00:24:50,680 --> 00:24:52,680 PLAYS, YOU WOULD SEE BOTH OF 487 00:24:52,680 --> 00:24:55,040 THOSE DEVICES IN REAL-TIME AND 488 00:24:55,040 --> 00:24:59,240 SO LET'S TRY THIS ONCE. 489 00:24:59,240 --> 00:25:01,040 SO, UNFORTUNATELY, WE ARE NOT 490 00:25:01,040 --> 00:25:02,800 ABLE TO SEE THE VIDEOS BUT IF 491 00:25:02,800 --> 00:25:04,960 YOU SAW THE VIDEO, WHAT YOU 492 00:25:04,960 --> 00:25:13,240 WOULD SEE IS DEVIS THAT IS ABOUT 493 00:25:13,240 --> 00:25:15,000 SEVERAL INCHES LONG THAT HAVE 494 00:25:15,000 --> 00:25:17,040 BLINKING LEDs AND ON THE SAME 495 00:25:17,040 --> 00:25:20,360 TIME OF THE INTERFACE YOU WOULD 496 00:25:20,360 --> 00:25:22,720 SEE A BRAIN PROBE FOR A MOUSE 497 00:25:22,720 --> 00:25:24,520 HAVING ITS LEDs CONTROLLED AT 498 00:25:24,520 --> 00:25:28,200 THE DISTANCE AND LEDs ARE THE 499 00:25:28,200 --> 00:25:29,960 ONLY FLASHY PART OF OUR DEVICE, 500 00:25:29,960 --> 00:25:32,200 WE HAVE SENSORS THAT ARE NOT SO 501 00:25:32,200 --> 00:25:35,360 VISUALLY APPEALING THAT WORK 502 00:25:35,360 --> 00:25:35,720 WELL. 503 00:25:35,720 --> 00:25:37,960 SO NOW, LET'S TRY THIS IN THE 504 00:25:37,960 --> 00:25:39,880 CONTEXT OF AN ACTUAL BEHAVIOR 505 00:25:39,880 --> 00:25:42,080 AND THE BEHAVE YEAR THAT WE ARE 506 00:25:42,080 --> 00:25:44,000 GOING TO USE WILL BE A SIMPLE 507 00:25:44,000 --> 00:25:45,080 REWARD TASK. 508 00:25:45,080 --> 00:25:48,160 IF YOU WERE TO CELL REWARD AT 509 00:25:48,160 --> 00:25:50,000 THE LEVEL OF THE BRAIN, YOU 510 00:25:50,000 --> 00:25:52,440 WOULD IMPLANT A DEVICE INTO ONE 511 00:25:52,440 --> 00:25:54,800 OF THE REWARD CENTERS AND SUCH 512 00:25:54,800 --> 00:25:57,440 AS AREAS AND THAT HAS HIGH 513 00:25:57,440 --> 00:25:58,760 POPULATION OF THE NEURONS AND 514 00:25:58,760 --> 00:26:03,680 THEN IF WE EXCITE THOSE NEURONS 515 00:26:03,680 --> 00:26:06,680 WE SEE AND WE CAN TEST IT IN THE 516 00:26:06,680 --> 00:26:08,320 PREFFENS IF ONE SIDE OF THE 517 00:26:08,320 --> 00:26:10,200 CHAMBER ANIMAL RESERVICE 518 00:26:10,200 --> 00:26:11,800 SIMULATION ON THE OTHER IT 519 00:26:11,800 --> 00:26:14,680 DOESN'T AND THEN IF THERE'S 520 00:26:14,680 --> 00:26:16,200 DOPAMINE INVOLVED IT WILL PREFER 521 00:26:16,200 --> 00:26:17,800 THIS STIMULATION SIDE AND THIS 522 00:26:17,800 --> 00:26:26,320 IS EXACTLY WHAT WE SEE AND IT'SA 523 00:26:26,320 --> 00:26:28,040 VERY ROBUST EFFECT. 524 00:26:28,040 --> 00:26:29,800 LET'S TRY A MORE INTERESTING 525 00:26:29,800 --> 00:26:30,640 EXPERIMENT. 526 00:26:30,640 --> 00:26:33,720 INSTEAD, LET'S STIMULATE VAGAL 527 00:26:33,720 --> 00:26:36,480 AT THE SMALL INTESTINE AND NOW 528 00:26:36,480 --> 00:26:39,840 ASK OUR ANIMAL TO ALSO CONDUCT 529 00:26:39,840 --> 00:26:43,560 THIS PLACE PREFERENCE ESSAY. 530 00:26:43,560 --> 00:26:45,080 WE SEE THE SAME THING. 531 00:26:45,080 --> 00:26:47,680 WE NOW SEE BY STIMULATING THIS 532 00:26:47,680 --> 00:26:54,120 ANIMAL AT THE LEVEL OF VAGAL 533 00:26:54,120 --> 00:26:56,480 AFFERANCE WE CAN MODULATE THEIR 534 00:26:56,480 --> 00:26:56,760 BEHAVIOR. 535 00:26:56,760 --> 00:26:59,680 THIS IS NOT NEWS TO SOME OF US 536 00:26:59,680 --> 00:27:02,640 THAT THE DOCTOR WHO HAS 537 00:27:02,640 --> 00:27:04,040 DISCOVERED A CIRCUIT THAT 538 00:27:04,040 --> 00:27:07,480 CONNECTS FROM THE GUT TO REWARD 539 00:27:07,480 --> 00:27:09,160 STRUCTURES IN THE BRAIN IN THE 540 00:27:09,160 --> 00:27:10,160 BRAIN. 541 00:27:10,160 --> 00:27:13,880 AND WE SEE CONSISTENT EFFECTS. 542 00:27:13,880 --> 00:27:15,200 SO NOW WE HAVE TALKED A LITTLE 543 00:27:15,200 --> 00:27:17,440 BIT ABOUT HOW WE CAN USE 544 00:27:17,440 --> 00:27:18,960 NEUROTECHNOLOGIES TO MODULATE 545 00:27:18,960 --> 00:27:20,520 NEURAL ACTIVITY AT THE LEVEL OF 546 00:27:20,520 --> 00:27:21,600 CIRCUITS AND THE LEVEL OF 547 00:27:21,600 --> 00:27:24,520 NEURONS AND WE CAN DO IT BOTH IN 548 00:27:24,520 --> 00:27:26,080 THE BRAIN AS WELL AS FOR ORGANS 549 00:27:26,080 --> 00:27:29,840 AND IF WE WERE TO UNDERSTAND 550 00:27:29,840 --> 00:27:31,640 FUNDAMENTAL BLOCKS OF NEURO 551 00:27:31,640 --> 00:27:33,280 COMMUNICATIONS, WE NEED TO START 552 00:27:33,280 --> 00:27:34,680 THINKING ABOUT OUR CHANNELS AND 553 00:27:34,680 --> 00:27:36,840 PROTEINS AND DO SO AT THE NANO 554 00:27:36,840 --> 00:27:37,200 SCALE. 555 00:27:37,200 --> 00:27:40,280 SO HOW DO WE MANIPULATE 556 00:27:40,280 --> 00:27:42,280 ACTIVITIES OF THOSE MOLECULES AT 557 00:27:42,280 --> 00:27:42,960 THEIR SCALE? 558 00:27:42,960 --> 00:27:44,800 FOR THAT WE NEED TO BE ABLE TO 559 00:27:44,800 --> 00:27:47,680 DELIVER A STIMULUS DEEP INTO THE 560 00:27:47,680 --> 00:27:50,760 BODY WITHOUT ACTUALLY AFFECTING 561 00:27:50,760 --> 00:27:51,960 THE BODY. 562 00:27:51,960 --> 00:27:54,600 AND THE ONLY FIELD THAT IS 563 00:27:54,600 --> 00:27:56,360 CAPABLE OF DOING THIS IS 564 00:27:56,360 --> 00:27:57,040 MAGNETIC FIELDS. 565 00:27:57,040 --> 00:27:59,640 IT'S THE ONLY FIELD THAT CAN 566 00:27:59,640 --> 00:28:00,400 PENETRATE ARBITRARILY DEEP INTO 567 00:28:00,400 --> 00:28:08,080 THE BODY AND IT'S NOT PERTURBED 568 00:28:08,080 --> 00:28:18,360 BY THE SKULL O EPI -- THEY'RE 569 00:28:18,360 --> 00:28:20,640 SMALLER THAN THE MRI MAGNATE 570 00:28:20,640 --> 00:28:24,520 INTO SOMETHING THAT BIOLOGY CAN 571 00:28:24,520 --> 00:28:24,800 UNDERSTAND. 572 00:28:24,800 --> 00:28:27,720 WE CAN PROVIDE SMALL MAGNETIC 573 00:28:27,720 --> 00:28:29,160 PART CALECHES THAT ABOUT 1/5,000 574 00:28:29,160 --> 00:28:31,480 OF YOUR HAIR THAT CONVERTS THOSE 575 00:28:31,480 --> 00:28:33,880 STIMULI INTO, FOR EXAMPLE, 576 00:28:33,880 --> 00:28:36,520 THERMAL STIMULUS TO MODULATE 577 00:28:36,520 --> 00:28:38,400 THERMO RECEPTORS AND THEY CAN 578 00:28:38,400 --> 00:28:40,960 NEURO CHEMICALS TO CONTROL CHEEP 579 00:28:40,960 --> 00:28:44,600 OWE RECEPTORS OR APPLY TENSION 580 00:28:44,600 --> 00:28:46,520 FORCES AND MODULATE RECEPTORS 581 00:28:46,520 --> 00:28:48,960 AND A NUMBER OF YEARS AGO, WE 582 00:28:48,960 --> 00:28:51,480 HAVE STARTED EXPLORING THIS IDEA 583 00:28:51,480 --> 00:28:53,360 BY FIRST DEMONSTRATING THAT WE 584 00:28:53,360 --> 00:28:56,800 CAN SYNTHESIZE NANOPARTICLES OF 585 00:28:56,800 --> 00:28:58,440 IRON OXIDE THAT HAVE A MAGNETIC 586 00:28:58,440 --> 00:29:00,440 MOMENT AND IF THAT MAGNETIC 587 00:29:00,440 --> 00:29:02,560 MOMENT IS SUBJECTED TO A 588 00:29:02,560 --> 00:29:04,000 MAGNETIC FIELD IT WILL ALIGN IN 589 00:29:04,000 --> 00:29:05,400 THE SAME DIRECTION AND WHEN WE 590 00:29:05,400 --> 00:29:06,600 SWITCH THE DIRECTION OF THE 591 00:29:06,600 --> 00:29:08,080 FIELD, THE MAGNETIC MOMENT WILL 592 00:29:08,080 --> 00:29:10,320 TRY TO SWITCH THE DIRECTION AS 593 00:29:10,320 --> 00:29:11,640 WELL AND IN THE PROCESS IT NEEDS 594 00:29:11,640 --> 00:29:16,120 TO OVERCOME AN ENERGY BARRIERS 595 00:29:16,120 --> 00:29:23,240 AND THAT GETS DISSIPATED AS HEAT 596 00:29:23,240 --> 00:29:27,920 AND IT CONTROLS TRIP V1 WHICH IS 597 00:29:27,920 --> 00:29:29,440 BROADLY EXPRESSED IN THE NERVOUS 598 00:29:29,440 --> 00:29:31,120 SYSTEM BUT ALSO IS AVAILABLE IN 599 00:29:31,120 --> 00:29:32,280 SOME PARTS OF THE CENTRAL 600 00:29:32,280 --> 00:29:33,120 NERVOUS SYSTEM. 601 00:29:33,120 --> 00:29:37,400 AND SO NOW, LET ME MAKE MY FINAL 602 00:29:37,400 --> 00:29:39,840 ATTEMPT PLAYING THIS MOVIE WHERE 603 00:29:39,840 --> 00:29:43,200 IF IT'S ACTUALLY WORKED, WHAT 604 00:29:43,200 --> 00:29:45,000 YOU WOULD SEE ON THE SIDE WHERE 605 00:29:45,000 --> 00:29:51,320 THE CELLS ARE SENSITIVE TO HEAT, 606 00:29:51,320 --> 00:29:54,040 THE PRESENCE OF THE 607 00:29:54,040 --> 00:29:56,040 NANOPARTICLES SENSITIVE THEM TO 608 00:29:56,040 --> 00:30:03,720 THE INPUT. 609 00:30:03,720 --> 00:30:05,960 IT ALLOWS US TO REMOTELY CONTROL 610 00:30:05,960 --> 00:30:08,040 HEAT SENSITIVE CELLS FROM A 611 00:30:08,040 --> 00:30:14,920 DISTANCE IN FREE LOW MOVING 612 00:30:14,920 --> 00:30:17,400 ANIMALS. 613 00:30:17,400 --> 00:30:27,920 NOW WE AND ALSO PRODUCES STRESS 614 00:30:55,240 --> 00:30:58,560 HORMONES AND INTERESTINGLY 615 00:30:58,560 --> 00:31:02,880 ENOUGH, BOTH COURT A KILL CELLS 616 00:31:02,880 --> 00:31:06,560 THAT PRODUCE CORTISOL AS WELL AS 617 00:31:06,560 --> 00:31:08,600 EPI NEFF RIN BOTH CONTAIN THE 618 00:31:08,600 --> 00:31:10,640 HEAT SENSITIVE CHANNELS AND 619 00:31:10,640 --> 00:31:17,160 THOSE HEAT SENSITIVE CHANNELS 620 00:31:17,160 --> 00:31:18,920 ARE PERMYABLE SO WE CAN APPLY 621 00:31:18,920 --> 00:31:20,840 OUR THERMAL STIMULATION TO 622 00:31:20,840 --> 00:31:23,840 HIJACK THIS ENTIRE CIRCUIT AND 623 00:31:23,840 --> 00:31:26,960 REMOTELY CONTROL RELEASE OF 624 00:31:26,960 --> 00:31:28,360 THOSE HORMONES THROUGH THE 625 00:31:28,360 --> 00:31:30,640 MAGNETIC FIELD AND IN DEED, WHAT 626 00:31:30,640 --> 00:31:33,000 WE FIND IN TISSUE CULTURES THAT 627 00:31:33,000 --> 00:31:34,880 IN THE PRESENCE OF MAGNETIC 628 00:31:34,880 --> 00:31:37,520 PARTICLES, MAGNETIC FIELDS IS 629 00:31:37,520 --> 00:31:40,480 STUFF AND TO EVOKE CALCIUM 630 00:31:40,480 --> 00:31:42,200 INFLUX INTO THOSE CELLS AND IT 631 00:31:42,200 --> 00:31:46,960 DEPENDS ON THE PRESENCE OF TRIP 632 00:31:46,960 --> 00:31:48,400 YO VAN CHANNEL BECAUSE IT 633 00:31:48,400 --> 00:31:49,920 ABOLISHES THIS EFFECT AND 634 00:31:49,920 --> 00:31:52,560 HOWEVER IF WE USE NON MAGNETIC 635 00:31:52,560 --> 00:31:54,080 PARTICLE CONTROLS WHICH DO NOT 636 00:31:54,080 --> 00:31:56,920 DISSIPATE HEAT, WE DO NOT SEE AN 637 00:31:56,920 --> 00:31:58,680 EFFECT OF MAGNETIC FIELD. 638 00:31:58,680 --> 00:32:02,760 WE CAN MOVE THIS IN VIVO AND TO 639 00:32:02,760 --> 00:32:05,120 GENETICALLY INTACT COMPLETELY 640 00:32:05,120 --> 00:32:07,120 UNMODIFIED RATS AND BASED ON OUR 641 00:32:07,120 --> 00:32:08,240 INJECTIONS, WHETHER INTO CORTEX 642 00:32:08,240 --> 00:32:11,520 OR THE MEDULLA, WE CAN RELEASE 643 00:32:11,520 --> 00:32:16,800 ON DEMAND EITHER COURTIC IN 644 00:32:16,800 --> 00:32:20,640 THOSE ANIMALS USING MAGNETIC 645 00:32:20,640 --> 00:32:26,920 FIELD NOTHING TOUCHES THOSE 646 00:32:26,920 --> 00:32:27,160 ANIMALS. 647 00:32:27,160 --> 00:32:30,400 WE CAN TAKE IT ONE STEP FURTHER 648 00:32:30,400 --> 00:32:32,840 AND LINK IT TO A RELEASE FROM 649 00:32:32,840 --> 00:32:35,280 NEURO CHEMICALS FROM LIPOSOMAL 650 00:32:35,280 --> 00:32:42,320 VAGAL AND ENDOW HEMO GENETICS SO 651 00:32:42,320 --> 00:32:45,200 BY LOADING TO DESIGNER 652 00:32:45,200 --> 00:32:52,120 RECEPTORS, INTO THOSE LINE SEEM 653 00:32:52,120 --> 00:32:54,560 IT WILL OPEN FORCED TO RELEASE 654 00:32:54,560 --> 00:32:55,600 THE DRUG. 655 00:32:55,600 --> 00:32:57,600 SO NOW WE CAN APPLY THIS METHOD 656 00:32:57,600 --> 00:33:03,080 TO CONTROL AGAIN, A RO REWARD 657 00:33:03,080 --> 00:33:03,320 CIRCUIT. 658 00:33:03,320 --> 00:33:13,840 WE FOR FOR A SWIM AT THE TEST. 659 00:33:30,920 --> 00:33:32,240 I WILL TELL WHAT YOU THIS VIDEO 660 00:33:32,240 --> 00:33:33,680 IS GOING TO LOOK LIKE. 661 00:33:33,680 --> 00:33:37,040 THIS VIDEO DEPICTS A MOUSE THAT 662 00:33:37,040 --> 00:33:39,360 IS HEAD AND SHOULDERS INSIDE A 663 00:33:39,360 --> 00:33:40,920 MAGNETIC COIL AND SWIMMING IN A 664 00:33:40,920 --> 00:33:41,280 BUCKET. 665 00:33:41,280 --> 00:33:42,920 YOU CANNOT SEE IT'S HEAD AND 666 00:33:42,920 --> 00:33:44,320 SHOULDERS BECAUSE THEY'RE NOT 667 00:33:44,320 --> 00:33:45,480 TRANSPARENT AND YOU WILL HAVE TO 668 00:33:45,480 --> 00:33:47,040 TAKE MY WORD FOR IT THAT THERE'S 669 00:33:47,040 --> 00:33:48,320 NOTHING TOUCHING THIS ANIMAL. 670 00:33:48,320 --> 00:33:53,080 IT LOOKS LIKE A WILD TYPE MOUSE. 671 00:33:53,080 --> 00:33:57,160 IT'S COMPLETELY FREE OF HARDWARE 672 00:33:57,160 --> 00:33:59,080 WITH THE EXCEPTION OF HAVING 673 00:33:59,080 --> 00:34:00,120 INJECTIONS. 674 00:34:00,120 --> 00:34:01,680 NOW, IF YOU TAKE A MOUSE AND PUT 675 00:34:01,680 --> 00:34:03,680 THEM NO A CUP OF WATER ON THE 676 00:34:03,680 --> 00:34:05,120 FIRST TRY THEY'RE MOTIVATED AND 677 00:34:05,120 --> 00:34:06,440 THEY'RE STRUGGLING TO GET OUT 678 00:34:06,440 --> 00:34:07,960 BUT IF YOU KEEP DOING THIS DAY 679 00:34:07,960 --> 00:34:11,120 AFTER DAY, THEY LEARN THAT THEY 680 00:34:11,120 --> 00:34:11,680 DON'T DROWN AND INSTEAD THEY 681 00:34:11,680 --> 00:34:13,040 JUST WAIT FOR RESEARCHER TO TAKE 682 00:34:13,040 --> 00:34:13,760 THEM OUT. 683 00:34:13,760 --> 00:34:15,280 THIS PROCESS IS CALLED 684 00:34:15,280 --> 00:34:15,680 ADAPTATION. 685 00:34:15,680 --> 00:34:17,200 SO IN THIS VIDEO YOU HAVE ONE OF 686 00:34:17,200 --> 00:34:20,040 THESE ADAPTED MICE THAT IS 687 00:34:20,040 --> 00:34:21,920 LITERALLY SITTING THERE IN A CUP 688 00:34:21,920 --> 00:34:30,200 OF WATER A RESEARCHER TO TAKE 689 00:34:30,200 --> 00:34:31,800 THEM OUT. 690 00:34:31,800 --> 00:34:34,600 INTO THEIR DOPAMINE BRAIN 691 00:34:34,600 --> 00:34:36,760 STRUCTURE AREAS AND DOPAMINE 692 00:34:36,760 --> 00:34:38,040 STARTS TO FLOW INTO THIS BRAIN 693 00:34:38,040 --> 00:34:39,680 AND THE MOUSE BECOMES 694 00:34:39,680 --> 00:34:41,120 EXCEPTIONALLY MOTIVATED TO SWIM 695 00:34:41,120 --> 00:34:43,040 OUT OF THE BUCKET. 696 00:34:43,040 --> 00:34:48,160 AND THIS IS QUITE REPRODUCE ABLE 697 00:34:48,160 --> 00:34:50,640 AND WE CAN REPEAT IT MULTIPLE 698 00:34:50,640 --> 00:34:52,280 DAYS IN THE ROW APPLIED TO 699 00:34:52,280 --> 00:34:55,720 DIFFERENT ESSAYS NOT ONLY ESSAYS 700 00:34:55,720 --> 00:34:57,240 SUCH AS FORM SWIM TEST BUT 701 00:34:57,240 --> 00:34:59,160 SOCIAL ESSAYS AND PREFFENS ESSAY 702 00:34:59,160 --> 00:35:02,120 ASK WE'LL SEE THE SAME RESULTS 703 00:35:02,120 --> 00:35:03,160 CONSISTENT WITH THE FUNCTION IN 704 00:35:03,160 --> 00:35:06,560 THE VTA. 705 00:35:06,560 --> 00:35:11,240 SO FINALLY, WE HAVE TALKED A LOT 706 00:35:11,240 --> 00:35:13,000 ABOUT MODULATING THERMO 707 00:35:13,000 --> 00:35:14,680 RECEPTORS AND CHEMO RECEPTORS 708 00:35:14,680 --> 00:35:16,120 AND HOW WE CAN TRANSLATE THOSE 709 00:35:16,120 --> 00:35:18,400 TOOLS TO THE ORGANS BEYOND THE 710 00:35:18,400 --> 00:35:19,920 BRAIN AND WE HAVE NOT TALKED 711 00:35:19,920 --> 00:35:22,680 ABOUT TRANSLATING MAGNETIC FIELD 712 00:35:22,680 --> 00:35:24,280 INTO MECHANICAL STIMULI WHICH 713 00:35:24,280 --> 00:35:27,040 MAY BE OF IMPORTANCE GIVEN THE 714 00:35:27,040 --> 00:35:29,520 FACT THAT THE RECEPTORS ARE 715 00:35:29,520 --> 00:35:32,160 EXPRESSED AT GREAT DEGREE IN 716 00:35:32,160 --> 00:35:35,040 ORGANS SUCH AS THE GUT AND MAY 717 00:35:35,040 --> 00:35:37,200 CONTROL PHENOMENON SUCH AS GUT 718 00:35:37,200 --> 00:35:41,760 PAIN OR SENSING THE SYSTEM. 719 00:35:41,760 --> 00:35:46,640 FOR THAT WE NEED TO LEARN TO 720 00:35:46,640 --> 00:35:48,160 APPLY FRACTIONS OF FORCE AND IT 721 00:35:48,160 --> 00:35:49,840 MAY SOUND SMALL TO YOU BUT IT'S 722 00:35:49,840 --> 00:35:54,080 HUGE AND THE MOLECULAR SCALE AND 723 00:35:54,080 --> 00:35:57,080 YOU NEED EITHER VERY LARGE 724 00:35:57,080 --> 00:35:59,000 MAGNETIC FIELD GRADIENTS SUCH AS 725 00:35:59,000 --> 00:36:07,360 THOSE USED IN MAGNETIC 1-888- MR 726 00:36:07,360 --> 00:36:09,560 WE NEED TO USE LARGE MAGNETIC 727 00:36:09,560 --> 00:36:11,040 PARTICLES AND THOSE ARE MAGNETS 728 00:36:11,040 --> 00:36:14,600 SO IF YOU TRY TO PUT THEM NO A 729 00:36:14,600 --> 00:36:16,240 SOLUTION, WHAT YOU THINK WILL 730 00:36:16,240 --> 00:36:17,280 HAPPEN THEY WILL ALL STICK TO 731 00:36:17,280 --> 00:36:19,520 EACH OTHER AND FORM GIANT BALLS 732 00:36:19,520 --> 00:36:21,480 THAT WILL BE USE LESS. 733 00:36:21,480 --> 00:36:24,200 HOW DO WE OVERCOME THIS PROBLEM? 734 00:36:24,200 --> 00:36:26,720 WE LEARN FROM MAGNETIC MEMBER 735 00:36:26,720 --> 00:36:28,240 ROW FIELDS WHERE IT'S KNOWN THAT 736 00:36:28,240 --> 00:36:32,960 WE CAN CREATE STRUCTURES WERE IN 737 00:36:32,960 --> 00:36:36,280 THE ABSENCE OF MAGNETIC FIELDS, 738 00:36:36,280 --> 00:36:37,800 ALL THE ATOMS LINEUP IN A CIRCLE 739 00:36:37,800 --> 00:36:39,800 AND THAT STATE IS CALLED THE 740 00:36:39,800 --> 00:36:40,960 VORTEX WHICH MEANS IN THE 741 00:36:40,960 --> 00:36:46,920 ABSENCE OF THE MAGNETIC FIELD, 742 00:36:46,920 --> 00:36:48,960 THEY'RE NOT ATTRACTED TO EACH 743 00:36:48,960 --> 00:36:51,200 OTHER AND WHEN WE HEAR FROM THE 744 00:36:51,200 --> 00:36:53,320 MAGNETIC FIELD IF IT'S VERY WEAK 745 00:36:53,320 --> 00:36:56,600 AND THE PARTICLES AND THE LINEUP 746 00:36:56,600 --> 00:37:00,200 IN PLANE AND NOW YOU HAVE A 747 00:37:00,200 --> 00:37:10,120 PEDESTRIAPETAL TO ACHIEVE THIS L 748 00:37:10,120 --> 00:37:12,280 MODULATION AND WE CAN TAKE THE 749 00:37:12,280 --> 00:37:14,360 DISK AND TARGET THEM TO THE 750 00:37:14,360 --> 00:37:15,400 MEMBRANES OF NEURONS IN THIS 751 00:37:15,400 --> 00:37:19,760 CASE TO SENSOR NEWER ALS FROM 752 00:37:19,760 --> 00:37:21,720 DOR SAL ROAD GANGLIA WHICH HAVE 753 00:37:21,720 --> 00:37:26,240 SCEPTER EXPRESSED IN THEM AND WE 754 00:37:26,240 --> 00:37:34,080 CAN APPLY WHAT IS GOING ON 755 00:37:34,080 --> 00:37:37,840 THE SIDE THAT CONTAINS NANO 756 00:37:37,840 --> 00:37:39,880 DISKS, YOU WILL SEE INFLUXES, 757 00:37:39,880 --> 00:37:41,000 FLASHES OF NEURONS IN RESPONSE 758 00:37:41,000 --> 00:37:44,480 TO A MAGNETIC FIELD WHILE IN THE 759 00:37:44,480 --> 00:37:47,360 ABSENCE OF A NANO DISK NOTHING 760 00:37:47,360 --> 00:37:48,600 HAPPENS AND INTERESTING THING 761 00:37:48,600 --> 00:37:51,440 ABOUT THIS EXPERIMENT IS UNLIKE 762 00:37:51,440 --> 00:37:54,320 EXPERTS I HAVE SHOWN YOU WITH 763 00:37:54,320 --> 00:37:56,040 THERMAL MODULATIONS WITH 764 00:37:56,040 --> 00:37:57,480 SOPHISTICATED ELECTRONICS, THIS 765 00:37:57,480 --> 00:38:00,640 CAN BE DONE WITH THE GUITAR 766 00:38:00,640 --> 00:38:01,360 AMPLIFIER AND WIRE. 767 00:38:01,360 --> 00:38:06,520 SO IT'S MUCH, MUCH SIMPLER. 768 00:38:06,520 --> 00:38:10,880 AND ANOTHER INTERESTING THING 769 00:38:10,880 --> 00:38:11,960 ABOUT MECHANICAL STIMULATION 770 00:38:11,960 --> 00:38:12,840 IT'S FAST. 771 00:38:12,840 --> 00:38:14,640 WE NO LONGER HAVE TO WAIT FOR 772 00:38:14,640 --> 00:38:16,480 HEAT DIS A PRECIPITATION OR DRUG 773 00:38:16,480 --> 00:38:18,040 DELIVERY WE GET AN EFFECT OF 774 00:38:18,040 --> 00:38:20,320 PULLING ON NEURONAL MEMBRANES 775 00:38:20,320 --> 00:38:24,680 AND ACTUALLY INFLUXES EVOKED ON 776 00:38:24,680 --> 00:38:27,520 MEDIATED BY THOSE SENSITIVE 777 00:38:27,520 --> 00:38:28,480 CHANNELS. 778 00:38:28,480 --> 00:38:30,600 SO NOW, WE HAVE FINALLY MADE IT 779 00:38:30,600 --> 00:38:33,440 TO THE END AND HOPEFULLY I HAVE 780 00:38:33,440 --> 00:38:35,800 CONVINCED YOU THAT BY LEVERAGING 781 00:38:35,800 --> 00:38:37,120 NEURO TECHNOLOGY EITHER AT THE 782 00:38:37,120 --> 00:38:40,080 MACRO AND MICRO SCALE SUCH AS 783 00:38:40,080 --> 00:38:41,480 MULTI FUNCTIONAL FIBERS WE'RE 784 00:38:41,480 --> 00:38:45,400 GOING FURTHER DOWN AND USING 785 00:38:45,400 --> 00:38:48,680 MAGNETIC TO MODULATE RECEPTORS 786 00:38:48,680 --> 00:38:52,000 WE CAN UNDERSTAND THE MULTITUDE 787 00:38:52,000 --> 00:38:54,120 OF SIGNALING SCALES IN THE 788 00:38:54,120 --> 00:38:55,560 ORGANS AND THE BRAIN AND 789 00:38:55,560 --> 00:38:57,320 ACTUALLY STARTING APPLYING IT TO 790 00:38:57,320 --> 00:39:00,040 OUR STUDIES OF INTEROCEPTION. 791 00:39:00,040 --> 00:39:01,560 I WOULD LIKE TO THANK MY 792 00:39:01,560 --> 00:39:03,000 TALENTED AND HARD-WORKING GROUP 793 00:39:03,000 --> 00:39:05,600 OF TRAINEES AS WELL AS THE 794 00:39:05,600 --> 00:39:16,000 GENEROUS SUPPORT FROM. 795 00:39:38,040 --> 00:39:40,200 >>ESPECIALLY PILING THROUGH 796 00:39:40,200 --> 00:39:41,760 WITH ALL THE TECHNICAL 797 00:39:41,760 --> 00:39:42,440 DIFFICULTIESES. 798 00:39:42,440 --> 00:39:46,000 WE DID HAVE ONE QUESTION FROM 799 00:39:46,000 --> 00:39:46,960 ON-LINE. 800 00:39:46,960 --> 00:39:51,080 AND REGARDING HEATING DAMAGE AND 801 00:39:51,080 --> 00:39:52,400 THEY WANTED TO KNOW IF YOU CAN 802 00:39:52,400 --> 00:39:53,680 FURTHER EXPLAIN HOW YOUR 803 00:39:53,680 --> 00:39:57,000 MAGNETIC HEATING MECHANISM 804 00:39:57,000 --> 00:39:59,600 SELECTIVE WITHOUT DAMA DAMAGINGR 805 00:39:59,600 --> 00:40:01,160 CELLS WITH THE ENERGY OR HEAT 806 00:40:01,160 --> 00:40:04,000 YOU ARE DISSIPATING, DOES THE 807 00:40:04,000 --> 00:40:05,320 TECHNIQUE ONLY WORK WHERE 808 00:40:05,320 --> 00:40:07,680 THERE'S SUBSTANTIAL AMOUNT OF 809 00:40:07,680 --> 00:40:10,680 TRP1 HEAT SENSITIVE CELLS? 810 00:40:10,680 --> 00:40:16,040 >>THAT'S A GREAT QUESTION SO IN 811 00:40:16,040 --> 00:40:18,160 FACT, WEOPERATE OUR MODULATION 812 00:40:18,160 --> 00:40:28,600 TO REACH TRIP V1 THRESHOLD 813 00:40:46,240 --> 00:40:49,840 >>IN THOSE EXPERIMENTS AND THEY 814 00:40:49,840 --> 00:40:51,640 HAVE OR OF COURSE CAN BE FULLY 815 00:40:51,640 --> 00:40:53,120 DISCOUNTED THAT IF YOU 816 00:40:53,120 --> 00:40:54,680 CONTINUOUSLY KEEP RAISING THE 817 00:40:54,680 --> 00:40:56,240 TEMPERATURE IN A GIVEN ORGAN, 818 00:40:56,240 --> 00:40:59,880 THAT YOU WILL START SEEING 819 00:40:59,880 --> 00:41:01,520 LONG-TERM EFFECTS TO LONG-TERM 820 00:41:01,520 --> 00:41:02,680 REMODELING, HOWEVER IN TERMS OF 821 00:41:02,680 --> 00:41:05,600 SHORT TERM DAMAGE OR ACTUALLY 822 00:41:05,600 --> 00:41:07,520 CLOSING, THIS IS NOT SOMETHING 823 00:41:07,520 --> 00:41:08,800 THAT IS GOING TO HAPPEN BECAUSE 824 00:41:08,800 --> 00:41:12,120 YOU WILL HAVE KEEP THE HEAT AT 825 00:41:12,120 --> 00:41:13,560 THAT LEVEL FOR 30 MINUTES TO 826 00:41:13,560 --> 00:41:24,080 START ACTUALLY KILLING NEURONS. 827 00:41:28,800 --> 00:41:35,640 >>MY QUESTION IS, WITH REGARDS 828 00:41:35,640 --> 00:41:36,560 TO REMOTE CONTROL TRANSDUCTION 829 00:41:36,560 --> 00:41:38,600 HOW FOCUSED CAN YOU MAKE THE 830 00:41:38,600 --> 00:41:40,040 MAGNET AND CAN YOU CONTROL FOR 831 00:41:40,040 --> 00:41:42,360 EXAMPLE DIFFERENT PARTS OF THE 832 00:41:42,360 --> 00:41:42,640 GI TRACT? 833 00:41:42,640 --> 00:41:48,400 >>THAT'S A WONDERFUL QUESTION, 834 00:41:48,400 --> 00:41:48,640 THANK YOU. 835 00:41:48,640 --> 00:41:53,120 THIS IS THE LOCALE TEE OF THE 836 00:41:53,120 --> 00:41:54,760 MAGNETIC STIMULATION DEPENDS ON 837 00:41:54,760 --> 00:41:56,440 TWO THINGS, THE PRESENCE OF 838 00:41:56,440 --> 00:41:58,160 CHANNEL MEDIATOR IN THE GIVEN 839 00:41:58,160 --> 00:42:00,440 TISSUE AND THAT YOU CAN BRING IN 840 00:42:00,440 --> 00:42:03,600 GENETICALLY OR RELY ON 841 00:42:03,600 --> 00:42:04,360 ENDOGENOUS EXPRESSION AND WHERE 842 00:42:04,360 --> 00:42:05,480 YOU PLACE THE PARTICLES AND SO 843 00:42:05,480 --> 00:42:09,760 THE WHOLE POINT OF MAGNETIC 844 00:42:09,760 --> 00:42:11,640 STIMULATION IS IT IS A EMPLOYED 845 00:42:11,640 --> 00:42:13,920 TO A MAN MALL PERFORMING A TASK 846 00:42:13,920 --> 00:42:15,440 IN AN ARENA AND ONLY THE CELLS 847 00:42:15,440 --> 00:42:16,720 THAT HAPPENED TO BE IN THE 848 00:42:16,720 --> 00:42:19,000 VICINITY ARE TARGETED BY THE 849 00:42:19,000 --> 00:42:20,640 PARTICLES WILL GET STIMULATED 850 00:42:20,640 --> 00:42:23,000 AND TARGETING IS A CHALLENGING 851 00:42:23,000 --> 00:42:25,640 QUESTION AND THAT IS WHY I WAS 852 00:42:25,640 --> 00:42:27,320 VERY FORTUNATE TO RECEIVE THE 853 00:42:27,320 --> 00:42:31,240 PIONEER AWARD TO SOLVE THAT 854 00:42:31,240 --> 00:42:34,800 PROBLEM AT THE ENABLE THIS SORT 855 00:42:34,800 --> 00:42:45,240 OF CELL TYPE SPECIFIC AND. 856 00:42:59,120 --> 00:43:00,680 >>I KNOW WE'RE BEHIND SCHEDULE 857 00:43:00,680 --> 00:43:04,040 AND I'LL LIKE TO INTRODUCE OUR 858 00:43:04,040 --> 00:43:07,240 OPERATOR, Dr. HEIKE 859 00:43:07,240 --> 00:43:07,680 MUENZBERG-GRUENING. 860 00:43:07,680 --> 00:43:09,360 >>WELCOME TO SESSION 1, 861 00:43:09,360 --> 00:43:09,640 EVERYONE. 862 00:43:09,640 --> 00:43:12,800 SO THIS IS ABOUT THE DIGESTIVE 863 00:43:12,800 --> 00:43:13,960 SYSTEM BRAIN CONNECTIONS AND 864 00:43:13,960 --> 00:43:16,120 WE'RE GOING TO HAVE FOUR 865 00:43:16,120 --> 00:43:17,600 SPEAKERS HERE AND SO THEY'RE 866 00:43:17,600 --> 00:43:18,800 GOING TO GO ONE AFTER THE OTHER 867 00:43:18,800 --> 00:43:21,360 AND I'M JUST GOING TO GO THROUGH 868 00:43:21,360 --> 00:43:23,000 THE HAWKS THAT WE HAVE RIGHT NOW 869 00:43:23,000 --> 00:43:24,160 AND EVERY PRESENTATION IS GOING 870 00:43:24,160 --> 00:43:28,440 TO BE 15 MINUTES IF WE HAVE TIME 871 00:43:28,440 --> 00:43:30,080 AND OTHERWISE WE'LL COLLECT 872 00:43:30,080 --> 00:43:31,560 QUESTIONS UNTIL THE END OF THE 873 00:43:31,560 --> 00:43:34,120 SESSION SO WE'RE GOING TO BE A 874 00:43:34,120 --> 00:43:35,800 JOINT QUESTION FOR 25 MINUTES. 875 00:43:35,800 --> 00:43:39,000 AND THE FIRST SPEAKER IS 876 00:43:39,000 --> 00:43:41,040 FUNCTIONAL NEUROCIRCUIT OF THOM 877 00:43:41,040 --> 00:43:48,720 AK BRAIN INTER OWE EXCEPTION 878 00:43:48,720 --> 00:43:51,520 WHICH IS ZHONGMING LIU AND THE 879 00:43:51,520 --> 00:43:55,720 SECOND FROM Dr. IVAN DE ARAUJO 880 00:43:55,720 --> 00:43:59,040 FROM THE ICAHN SCHOOL OF 881 00:43:59,040 --> 00:44:00,880 MEDICINE AT MOUNT SINAI AND THE 882 00:44:00,880 --> 00:44:03,800 NEXT IS GUT-TO-BRAIN CIRCUITS 883 00:44:03,800 --> 00:44:06,200 UNDER LIG FLUID FROM Dr. YUKI 884 00:44:06,200 --> 00:44:07,880 OKA AND THE FOURTH SPEAKER IS 885 00:44:07,880 --> 00:44:10,360 GOING TO ABOUT FUNCTIONAL 886 00:44:10,360 --> 00:44:12,600 IDENTIFICATION OF VAGAL SENSORY 887 00:44:12,600 --> 00:44:16,040 NEURONS INNER RATE ISING THE 888 00:44:16,040 --> 00:44:22,520 LIVER FROM Dr. YOUNG-HWAN JO. 889 00:44:22,520 --> 00:44:32,960 PLEASE, TAKE THE FLOOR. 890 00:44:40,000 --> 00:44:41,320 FOR ON-LINE QUESTIONS WHICH 891 00:44:41,320 --> 00:44:42,480 REFER TO EACH SPEAKER YOU ASK 892 00:44:42,480 --> 00:44:43,680 THE QUESTION FOR THE END 893 00:44:43,680 --> 00:44:45,800 QUESTION AND ANSWER SO MAYBE 894 00:44:45,800 --> 00:44:47,160 IT'S ONE FOR SPEAKER ONE THAT 895 00:44:47,160 --> 00:44:54,720 WOULD BE GREAT. 896 00:44:54,720 --> 00:44:56,840 >>THANK YOU FOR THE 897 00:44:56,840 --> 00:44:58,200 INTRODUCTION, I HOPE THE SLIDES 898 00:44:58,200 --> 00:44:59,720 DISPLAY PROPERLY ON THE ZOOM 899 00:44:59,720 --> 00:44:59,960 SIDE. 900 00:44:59,960 --> 00:45:01,040 IT'S MY GREAT PLEASURE TO BE A 901 00:45:01,040 --> 00:45:02,840 PART OF THIS MEETING AND I HAVE 902 00:45:02,840 --> 00:45:04,520 RECEIVED A FUND TO GO DO THIS 903 00:45:04,520 --> 00:45:08,080 PROJECT AND THE PROJECT FUNCTION 904 00:45:08,080 --> 00:45:14,120 NEUROCIRCUITS OF STOMACH-BRAIN 905 00:45:14,120 --> 00:45:14,440 INTEROCEPTION. 906 00:45:14,440 --> 00:45:16,320 WE BOTH OF US WILL BE HAPPY TO 907 00:45:16,320 --> 00:45:18,840 ANSWER QUESTIONS AND JOINING ME 908 00:45:18,840 --> 00:45:24,280 IS JIANDE AN CHEN. 909 00:45:24,280 --> 00:45:25,640 OUR PROJECTS ARE TRYING TO 910 00:45:25,640 --> 00:45:26,920 ADDRESS THE QUESTIONS OF HOW THE 911 00:45:26,920 --> 00:45:28,600 BRAIN AND INTERACTS WITH THE 912 00:45:28,600 --> 00:45:30,360 STOMACH AND WE ARE LOOKING AT 913 00:45:30,360 --> 00:45:32,600 THIS FROM THE LEVEL OF FUNCTION 914 00:45:32,600 --> 00:45:42,920 NEUROCIRCUITS AND 915 00:45:57,640 --> 00:46:03,920 IT'S PROPAGATING ALONG THE 916 00:46:03,920 --> 00:46:08,120 STOMACH AND ALSO THE 917 00:46:08,120 --> 00:46:09,400 ACCOMMODATION THAT ALLOWS THE 918 00:46:09,400 --> 00:46:10,720 STOMACH TO STORE THE FOODS AND 919 00:46:10,720 --> 00:46:13,560 HOW TO STOMACH AND HANDLES 920 00:46:13,560 --> 00:46:17,040 DIFFERENT NUTRIENTS. 921 00:46:17,040 --> 00:46:19,120 AND THEN, THIS TYPE OF PROJECTS 922 00:46:19,120 --> 00:46:21,000 THAT INVOLVES A LOT OF DIFFERENT 923 00:46:21,000 --> 00:46:22,640 EXPERTISE, WE HAVE EXPERTS IN 924 00:46:22,640 --> 00:46:28,880 MRI AND ELECTRIC 925 00:46:28,880 --> 00:46:39,160 PHYSIOLOGY AND. 926 00:49:13,240 --> 00:49:16,440 >>CAN BE CONFIRMED WITH RESPECT 927 00:49:16,440 --> 00:49:18,680 TO THE DEFERENTIAL 928 00:49:18,680 --> 00:49:20,800 CONSTITUTIONAL VAGAL AND WE CAN 929 00:49:20,800 --> 00:49:23,280 CUT THE VEGAS NERVE SO SEE HOW 930 00:49:23,280 --> 00:49:25,920 MUCH THE ACTIVATION WOULD 931 00:49:25,920 --> 00:49:28,840 DIMINISH AND WOVE FOUND A 932 00:49:28,840 --> 00:49:30,240 SUBSTANTIAL LESS BRAIN 933 00:49:30,240 --> 00:49:37,960 ACTIVATION WHEN WE CUT THE NERVE 934 00:49:37,960 --> 00:49:42,240 AND IT WILL BE USED OVER THE 935 00:49:42,240 --> 00:49:44,480 COURSE OF OUR PROJECT AND WE 936 00:49:44,480 --> 00:49:46,840 ALSO ACTUALLY LOOK AT THE 937 00:49:46,840 --> 00:49:48,040 INTRINSIC BRAIN NETWORKS AND 938 00:49:48,040 --> 00:49:50,240 AGAIN THIS IS USING A TECHNIQUE 939 00:49:50,240 --> 00:49:52,480 CALLED RESTING STATE FUNCTIONAL 940 00:49:52,480 --> 00:49:59,320 CONNECTIVELY AND USED IN HUMANS 941 00:49:59,320 --> 00:50:05,960 AND AND HOWEVER IT'S NOT BEEN 942 00:50:05,960 --> 00:50:07,600 RELATED TO THE INTRO PROCESSES 943 00:50:07,600 --> 00:50:10,080 AND WE ACTUALLY FURTHER ACTUALLY 944 00:50:10,080 --> 00:50:11,600 LOOKED AT THIS AND THE WAKE 945 00:50:11,600 --> 00:50:14,560 ANIMALS USING A PRODUCT 946 00:50:14,560 --> 00:50:17,600 ESTABLISHED IN OUR COLLABORATOR 947 00:50:17,600 --> 00:50:19,480 JOB AT PEN STATE AND WE TRAINED 948 00:50:19,480 --> 00:50:21,760 ANIMALS TO STAY AWAKE IN MRI 949 00:50:21,760 --> 00:50:23,080 WHILE WE SCAN THEM AND IT TAKES 950 00:50:23,080 --> 00:50:24,320 ONE WEEK OF TRAINING AND OVER 951 00:50:24,320 --> 00:50:25,480 THE COURSE OF ONE WEEK THE 952 00:50:25,480 --> 00:50:29,240 ANIMAL IS RELATIVELY STILL AND 953 00:50:29,240 --> 00:50:32,120 RELATIVE AND LOW AND INSIDE OF 954 00:50:32,120 --> 00:50:38,400 MRI FOR AN HOUR. 955 00:50:38,400 --> 00:50:39,920 AND SINCE THE START OF THIS 956 00:50:39,920 --> 00:50:45,400 PROJECT WE LOOKED AT THIS 957 00:50:45,400 --> 00:50:47,440 INTRINSIC FUNCTIONAL AND IS THE 958 00:50:47,440 --> 00:50:49,440 DORRAL VAGAL COMPLEX IN THE 959 00:50:49,440 --> 00:50:52,640 BRAIN STEM WHERE THE INFLOW AND 960 00:50:52,640 --> 00:50:54,640 OUTFLOW INFORMATION AND A LOT OF 961 00:50:54,640 --> 00:50:56,520 VISCERAL ORGANS AND THEY WILL 962 00:50:56,520 --> 00:50:58,520 PASS THROUGH AND WE LOOK AT THE 963 00:50:58,520 --> 00:51:00,440 INTRINSIC FUNCTIONAL ACTIVITY TO 964 00:51:00,440 --> 00:51:03,520 THE AND WE HAVE IDEA NUMBER OF 965 00:51:03,520 --> 00:51:07,040 AREAS SIMILAR AND WE UNDERSTOOD 966 00:51:07,040 --> 00:51:09,320 ABOUT AND THE NET WICK AND 967 00:51:09,320 --> 00:51:13,480 INVOLVING THE SINGLE CORTEX 968 00:51:13,480 --> 00:51:15,320 HYPOTHALIMUS, THALAMUS AND SOME 969 00:51:15,320 --> 00:51:18,560 OF THE BRAIN STEM NUCLEUS AND 970 00:51:18,560 --> 00:51:23,840 WE'RE TRYING TO UNDERSTAND THE 971 00:51:23,840 --> 00:51:24,240 FUNCTIONAL ROWS. 972 00:51:24,240 --> 00:51:34,720 IT GIVES US ANOTHER AND WE CAN 973 00:51:38,360 --> 00:51:40,920 SEE THE STOMACH MOVEMENT THAT 974 00:51:40,920 --> 00:51:43,920 THE MOVEMENT OF THE ENTIRE GI 975 00:51:43,920 --> 00:51:45,720 TRACT USING MRI AND FORTUNATELY 976 00:51:45,720 --> 00:51:50,320 THIS TIME THE VIDEO PLAYS. 977 00:51:50,320 --> 00:51:52,800 WE CAN LOOK AT NERVE ACTIVITY 978 00:51:52,800 --> 00:51:55,200 AND ONE WAY TO LOOK AT THEN 979 00:51:55,200 --> 00:51:57,440 INJECT THE CONTRAST AGENT INTO 980 00:51:57,440 --> 00:52:02,480 THE GANGLION AND TO THIS TYPE OF 981 00:52:02,480 --> 00:52:12,960 CONTRAST CONTAINS AND WE TEST 982 00:52:19,800 --> 00:52:21,200 THE FEASIBILITY OF THIS BY 983 00:52:21,200 --> 00:52:23,320 SAYING THAT IF WE INJECTED THE 984 00:52:23,320 --> 00:52:26,120 CONTRAST AGENT INTO THE LEFT 985 00:52:26,120 --> 00:52:27,520 GANGLION WE'LL SEE THE LEFT 986 00:52:27,520 --> 00:52:29,560 LIGHT UP AND WE ALSO SEE SOME OF 987 00:52:29,560 --> 00:52:31,800 THE DOWNSTREAM NUCLEUS LIGHT UP 988 00:52:31,800 --> 00:52:33,560 SO WE'LL CONTINUE EXPLORING THIS 989 00:52:33,560 --> 00:52:35,240 TECHNIQUE FOR MAPPING THE 990 00:52:35,240 --> 00:52:36,880 CENTRAL CIRCUITS THROUGH THE 991 00:52:36,880 --> 00:52:38,200 ASCENDING PATHWAYS. 992 00:52:38,200 --> 00:52:40,680 AND THIS IS NOT JUST A TRACING 993 00:52:40,680 --> 00:52:44,480 BUT IT'S ALSO A FUNCTION MATCHES 994 00:52:44,480 --> 00:52:45,320 OF THE NERVE TECH TO HAVE WHEN 995 00:52:45,320 --> 00:52:49,080 WE UP REGULATE THE VEGAS NERVE 996 00:52:49,080 --> 00:52:52,440 STIMULATING THE VEGAS NERVE 997 00:52:52,440 --> 00:52:54,280 THERE'S MORE UPTAKE AND LEVEL OF 998 00:52:54,280 --> 00:52:55,960 NTS AND WE ALSO ANTICIPATE THAT 999 00:52:55,960 --> 00:53:00,040 WHEN WE ACTUALLY PERTURBED THE 1000 00:53:00,040 --> 00:53:02,440 CIRCUITS IN DIFFERENT WAYS WE'LL 1001 00:53:02,440 --> 00:53:03,640 MATCH OUT DIFFERENT FUNCTIONS OF 1002 00:53:03,640 --> 00:53:08,920 CIRCUITS IN THE BRAIN. 1003 00:53:08,920 --> 00:53:10,760 WE CAN ALSO RECORD FROM THE NTS 1004 00:53:10,760 --> 00:53:17,240 NEURONS AND RESPONDING TO THE 1005 00:53:17,240 --> 00:53:17,920 GASTRIC INTEROCEPTION SO WE CAN 1006 00:53:17,920 --> 00:53:20,080 LOOK AT IT IN THE MULTI UNIT 1007 00:53:20,080 --> 00:53:21,480 LEVELS AND WHAT IS OF PARTICULAR 1008 00:53:21,480 --> 00:53:24,080 INTEREST WHEN WE APPLY THE 1009 00:53:24,080 --> 00:53:27,800 STIMULATION TO A TYPE OF VAGAL 1010 00:53:27,800 --> 00:53:33,000 AVENUE REASONS ON THE STOMACH, 1011 00:53:33,000 --> 00:53:37,200 THE ACTIVITIES AND WE APPLY THE 1012 00:53:37,200 --> 00:53:38,360 STIMULATION AND SURPRISINGLY WE 1013 00:53:38,360 --> 00:53:40,960 FIND THIS TYPE OF NEURONS ARE 1014 00:53:40,960 --> 00:53:42,960 HIGHLY SENSITIVE TO THE OREN 1015 00:53:42,960 --> 00:53:53,440 TAKE OF THE STIMULATION AND 1016 00:53:53,720 --> 00:53:54,760 STIMULATE THE STOMACH AND MAP 1017 00:53:54,760 --> 00:53:56,960 OUT THE FUNCTIONAL CIRCUITS 1018 00:53:56,960 --> 00:53:59,560 INVOLVED IN THE GASTRO 1019 00:53:59,560 --> 00:53:59,960 INTEROCEPTION. 1020 00:53:59,960 --> 00:54:02,080 AND THIS IS A TRUE FOR TWO 1021 00:54:02,080 --> 00:54:08,200 DIFFERENT AND ONE IS THE VAGAL 1022 00:54:08,200 --> 00:54:09,960 FOR THE MUSCLE AND THE OTHER IS 1023 00:54:09,960 --> 00:54:12,160 THE CIRCULAR MUSCLES AND FOR 1024 00:54:12,160 --> 00:54:14,960 THOSE CASES, THE ORIENTATION 1025 00:54:14,960 --> 00:54:15,800 SELECTIVITY IS TRUE. 1026 00:54:15,800 --> 00:54:17,760 NOW LOOKING AT THE SPONTANEOUS 1027 00:54:17,760 --> 00:54:19,560 STOMACH IN THE BRAIN 1028 00:54:19,560 --> 00:54:21,440 INTERACTIONS THAT WITHOUT ANY 1029 00:54:21,440 --> 00:54:22,520 STIMULATION THAT ACTUALLY THE 1030 00:54:22,520 --> 00:54:24,320 STOMACH AND THE BRAIN INTERACTS 1031 00:54:24,320 --> 00:54:26,240 IN REAL-TIME AND THIS IS A HUMAN 1032 00:54:26,240 --> 00:54:31,400 STUDY BY A GROUP IN FRANCE AND 1033 00:54:31,400 --> 00:54:34,120 LED AND THEY RECORD THE GASTRIC 1034 00:54:34,120 --> 00:54:36,200 SLOW WAVE IN THE STOMACH THE 1035 00:54:36,200 --> 00:54:40,200 BRAIN ACTIVITY IS FACE LOCKED TO 1036 00:54:40,200 --> 00:54:42,040 THE GASTRO RHYTHMS AND WE'RE 1037 00:54:42,040 --> 00:54:43,640 INSPIRED BY THAT SO WE END UP 1038 00:54:43,640 --> 00:54:45,440 REPLICATING THIS STUDY IN THE 1039 00:54:45,440 --> 00:54:47,920 RAT MODEL SO WE RECORD A GASTRIC 1040 00:54:47,920 --> 00:54:58,520 SLOW WAVE AND REASON AND PROFESR 1041 00:54:58,520 --> 00:55:00,040 JIANDE CHEN IS AN EXPERT IN 1042 00:55:00,040 --> 00:55:00,360 THIS. 1043 00:55:00,360 --> 00:55:01,560 WHAT PEOPLE REPORT IN HUMANS 1044 00:55:01,560 --> 00:55:04,640 THERE'S A REAL-TIME GUT RING 1045 00:55:04,640 --> 00:55:07,520 INTERACTION AND ITSELF THE 1046 00:55:07,520 --> 00:55:09,880 STOMACH BRAIN COHERENCE IN TERMS 1047 00:55:09,880 --> 00:55:10,880 OF THE SIGNALS. 1048 00:55:10,880 --> 00:55:13,600 AND WE ARE INTERESTED IN WHAT IS 1049 00:55:13,600 --> 00:55:15,240 THIS INTERACTION SO WE ACTUALLY 1050 00:55:15,240 --> 00:55:16,960 CUT THE NERVE AND TRIED TO SEE 1051 00:55:16,960 --> 00:55:19,040 HOW MUCH THE VEGAS AFTER 1052 00:55:19,040 --> 00:55:20,040 CONTRIBUTING TO INTERSECTION. 1053 00:55:20,040 --> 00:55:22,760 THE SURPRISINGLY WHEN WE CUT THE 1054 00:55:22,760 --> 00:55:24,920 NERVE THIS INTERACTION IS ALMOST 1055 00:55:24,920 --> 00:55:27,560 GONE AND SO THIS ACTUALLY 1056 00:55:27,560 --> 00:55:30,720 SUGGESTS A CENTRAL ROLE OF THE 1057 00:55:30,720 --> 00:55:31,920 VEGAS IMMEDIATE STOMACH AND 1058 00:55:31,920 --> 00:55:33,560 BRAIN AND WHEN WE CUT THE NERVE 1059 00:55:33,560 --> 00:55:36,520 AND WE SEE THE STOMACH STILL CON 1060 00:55:36,520 --> 00:55:38,000 TRACTS AND THE REASON IT EXISTS 1061 00:55:38,000 --> 00:55:39,680 SO THIS RHYTHM IS REALLY A 1062 00:55:39,680 --> 00:55:41,600 REASON THAT THE PASSING FROM THE 1063 00:55:41,600 --> 00:55:43,000 STOMACH INTO THE BRAIN AND NOT 1064 00:55:43,000 --> 00:55:45,080 THE OTHER WAY AROUND. 1065 00:55:45,080 --> 00:55:47,760 NOW WE'RE LOOKING AT THE GASTRIC 1066 00:55:47,760 --> 00:55:49,840 SLOW WAVES AND WE'RE LOOKING AT 1067 00:55:49,840 --> 00:55:52,240 THE ACTIVITY IN THIS CASE THAT 1068 00:55:52,240 --> 00:55:58,680 WE PUT THE THE CON VAXES IN 1069 00:55:58,680 --> 00:56:00,520 REAL-TIME AND IT'S THE WE'RE 1070 00:56:00,520 --> 00:56:03,240 GOING TO BEGIN TO LOOK AT A 1071 00:56:03,240 --> 00:56:06,080 MECHANICAL ACTIVITY AND HOW IT'S 1072 00:56:06,080 --> 00:56:07,160 SYNCHRONIZED WITH BRAIN ACTIVITY 1073 00:56:07,160 --> 00:56:07,800 IN REAL-TIME. 1074 00:56:07,800 --> 00:56:09,160 I RAN OUT OF TIME. 1075 00:56:09,160 --> 00:56:11,120 THIS TECHNOLOGY ARE TRANSLATABLE 1076 00:56:11,120 --> 00:56:15,400 TO HUMANS AND ACTUALLY AS PART 1077 00:56:15,400 --> 00:56:18,400 OF TRYING TO LOOK AT THIS IN A 1078 00:56:18,400 --> 00:56:21,320 HUMANS AS WELL AND RECORDING A 1079 00:56:21,320 --> 00:56:23,880 LOT OF ORGAN FUNCTIONS THE 1080 00:56:23,880 --> 00:56:25,280 HEART, LUNG AND THE AROSAL 1081 00:56:25,280 --> 00:56:28,400 SIGNALS AND EMOTIONAL RESPONSES 1082 00:56:28,400 --> 00:56:29,280 AND HOW THEY'RE MAPPED OUT INTO 1083 00:56:29,280 --> 00:56:29,920 THE BRAIN. 1084 00:56:29,920 --> 00:56:31,480 WITH THAT I'D LIKE TO CONCLUDE. 1085 00:56:31,480 --> 00:56:33,200 I HOPE I CONVINCED YOU THAT WE 1086 00:56:33,200 --> 00:56:34,920 HAVE A NUMBER OF DIFFERENT 1087 00:56:34,920 --> 00:56:36,440 TECHNOLOGIES AND FOR STUDYING 1088 00:56:36,440 --> 00:56:39,880 THE STOMACH-BRAIN INTERACTION 1089 00:56:39,880 --> 00:56:48,000 FROM REAR TIME AND THE VAGUS AND 1090 00:56:48,000 --> 00:56:50,440 GASTRIC NEURONS AT THE NTS ARE 1091 00:56:50,440 --> 00:56:51,400 OR'EN TAKE SELECTIVE AND WE CAN 1092 00:56:51,400 --> 00:56:53,600 DO IT IN AWAKE ANIMALS AND WE'RE 1093 00:56:53,600 --> 00:56:54,600 LOOKING FORWARD TO THE 1094 00:56:54,600 --> 00:56:58,560 OPPORTUNITY TO DO THIS IN HUMANS 1095 00:56:58,560 --> 00:56:59,160 AS WELL. 1096 00:56:59,160 --> 00:57:02,680 [APPLAUSE] 1097 00:57:02,680 --> 00:57:04,680 THANK YOU, I THINK WE HAVE TIME 1098 00:57:04,680 --> 00:57:08,920 FOR ONE QUESTION AND IF Dr. 1099 00:57:08,920 --> 00:57:10,480 ARAUJO IS ALREADY MOVING UP AND 1100 00:57:10,480 --> 00:57:13,320 OPEN HIS PRESENTATION SO WE CAN 1101 00:57:13,320 --> 00:57:17,040 HAVE ONE QUESTION FOR Dr. LIU. 1102 00:57:17,040 --> 00:57:18,360 ANY QUESTIONS IN THE ROOM OR IN 1103 00:57:18,360 --> 00:57:25,080 THE CHAT ROOM? 1104 00:57:25,080 --> 00:57:26,120 I HAVE A QUESTION. 1105 00:57:26,120 --> 00:57:28,760 WHAT DO YOU THINK WOULD BE THE 1106 00:57:28,760 --> 00:57:30,920 FUNCTION OF THE -- FOR EXAMPLE, 1107 00:57:30,920 --> 00:57:34,360 FOR BARIATRIC SURGERY, WHAT 1108 00:57:34,360 --> 00:57:36,480 WOULD THAT TRANSLATE? 1109 00:57:36,480 --> 00:57:38,680 WOULD IT MODIFY THE AMOUNT OF 1110 00:57:38,680 --> 00:57:39,680 FOOD INTAKE? 1111 00:57:39,680 --> 00:57:40,880 BODY WEIGHT, WHAT IS YOUR 1112 00:57:40,880 --> 00:57:41,240 SUGGESTION HERE? 1113 00:57:41,240 --> 00:57:43,360 >>THE SURGICAL PROCESS HAS 1114 00:57:43,360 --> 00:57:46,320 DEFINITELY IMPLICATIONS AND WE 1115 00:57:46,320 --> 00:57:48,440 ACTUALLY, SOME OF THE STUDIES IN 1116 00:57:48,440 --> 00:57:50,440 ACUTE SETTINGS AND WE HAVE A 1117 00:57:50,440 --> 00:57:52,600 SHAM CONTROL AND SOME OF THIS 1118 00:57:52,600 --> 00:57:55,320 ARE INVOLVING THE CHRONICLE 1119 00:57:55,320 --> 00:57:56,640 IMPLANTATION SO HOPEFULLY IN 1120 00:57:56,640 --> 00:57:58,720 THOSE CHRONIC SITUATIONS, THE 1121 00:57:58,720 --> 00:58:03,040 IMPACT OF THE SURGERY IS MORE 1122 00:58:03,040 --> 00:58:04,400 CONTROLLABLE AND IT WILL BE LESS 1123 00:58:04,400 --> 00:58:05,360 OF A CONCERN. 1124 00:58:05,360 --> 00:58:07,760 >>IT'S AMAZING HOW PRECISE YOU 1125 00:58:07,760 --> 00:58:09,280 CAN ALSO PINPOINT THESE BRAIN 1126 00:58:09,280 --> 00:58:11,520 AREAS AND I MEAN, IT WAS USUALLY 1127 00:58:11,520 --> 00:58:15,560 YOU CANNOT GO THAT DEEP, RIGHT. 1128 00:58:15,560 --> 00:58:23,400 >>WEST RESOLUTION ABOUT A 1129 00:58:23,400 --> 00:58:25,680 $.2 MILLION RESOLUTION RAT 1130 00:58:25,680 --> 00:58:26,000 BRAIN. 1131 00:58:26,000 --> 00:58:28,200 IT'S NOT HIGH ENOUGH BUT IT WILL 1132 00:58:28,200 --> 00:58:29,600 GIVE US AN IDEA OF WHICH WILL BE 1133 00:58:29,600 --> 00:58:32,400 INVOLVED IN THE GASTRO 1134 00:58:32,400 --> 00:58:32,720 INTEROCEPTION. 1135 00:58:32,720 --> 00:58:38,840 >>VERY EXCITING. 1136 00:58:38,840 --> 00:58:40,600 >>GO AHEAD. 1137 00:58:40,600 --> 00:58:45,040 >>SO, THANK YOU SO MUCH FOR THE 1138 00:58:45,040 --> 00:58:46,920 INVITATION AND FOR BEING PART OF 1139 00:58:46,920 --> 00:58:47,680 THIS PROGRAM. 1140 00:58:47,680 --> 00:58:49,280 SO, I'LL BE SPEAKING A LITTLE 1141 00:58:49,280 --> 00:58:55,160 BIT ABOUT THE SPINAL GUT-BRAIN 1142 00:58:55,160 --> 00:58:55,600 PATHWAY. 1143 00:58:55,600 --> 00:59:00,200 SO, IN TERMS OF RATIONALE, OVER 1144 00:59:00,200 --> 00:59:03,400 THE LAST 50 OR 60 YEARS, WE 1145 00:59:03,400 --> 00:59:05,800 FORMED THE FIRM IMPRESSION THAT 1146 00:59:05,800 --> 00:59:10,120 THE MAIN CONDUCT OF INFORMATION 1147 00:59:10,120 --> 00:59:17,160 FROM THE GUT TO THE BRAIN IS THE 1148 00:59:17,160 --> 00:59:27,440 HAVING US NERVE. 1149 00:59:29,360 --> 00:59:30,520 WITH BLOATING AND FULLNESS THAT 1150 00:59:30,520 --> 00:59:33,480 IS PRESUMABLY A FUNCTIONAL UNIT 1151 00:59:33,480 --> 00:59:37,880 IN THE CONTROL OF FOOD INTAKE. 1152 00:59:37,880 --> 00:59:40,200 HOWEVER, MORE CAREFUL ANALYSIS 1153 00:59:40,200 --> 00:59:43,400 OF THE DATA ON THE VAGUS NERVE 1154 00:59:43,400 --> 00:59:45,640 ON VAGUS NERVE LESIONS OVER THE 1155 00:59:45,640 --> 00:59:50,800 YEARS, DO NOT SHOW AT ALL 1156 00:59:50,800 --> 00:59:53,080 ACTUALLY THAT DISRUPTING THE 1157 00:59:53,080 --> 00:59:54,560 NERVE WILL LEAD TO A GREATER 1158 00:59:54,560 --> 00:59:57,920 INTAKE OR TO AN ACCESS OF 1159 00:59:57,920 --> 00:59:59,520 GASTRIC FULLNESS AS WOULD BE 1160 00:59:59,520 --> 01:00:02,840 EXPECTED, IF THE SYSTEM WOULD BE 1161 01:00:02,840 --> 01:00:05,560 PERFORMING SUCH FUNCTIONS. 1162 01:00:05,560 --> 01:00:08,280 SO, ONE POSSIBILITY TO EXPLAIN 1163 01:00:08,280 --> 01:00:11,160 HOW WE FORM THIS CONSCIOUS CLEAR 1164 01:00:11,160 --> 01:00:13,120 PERCEPTION OF FULLNESS AND 1165 01:00:13,120 --> 01:00:16,400 GASTRIC DISTINCTION IS THAT 1166 01:00:16,400 --> 01:00:23,600 ANOTHER LESS STUDIED GUT BRAIN 1167 01:00:23,600 --> 01:00:24,840 PATHWAY THE SPINE AT SENSORY 1168 01:00:24,840 --> 01:00:26,480 PATHWAY MAY BE INVOLVED IN 1169 01:00:26,480 --> 01:00:27,040 CESSATION. 1170 01:00:27,040 --> 01:00:29,920 ARGUING FOR THIS POSSIBILITY IS 1171 01:00:29,920 --> 01:00:32,400 ANOTHER ORGAN, THE BLADDER. 1172 01:00:32,400 --> 01:00:33,920 SO THE BLADDER IS VERY SIMILAR 1173 01:00:33,920 --> 01:00:37,040 TO THE STOMACH IN SENSORY TERMS 1174 01:00:37,040 --> 01:00:39,280 IN MANY WAYS. 1175 01:00:39,280 --> 01:00:41,160 SO, WE HAVE A CONSCIOUS 1176 01:00:41,160 --> 01:00:42,720 PERCEPTION OF THE STATE OF THE 1177 01:00:42,720 --> 01:00:48,200 BLADDER AND IT CAN GO FROM MILD 1178 01:00:48,200 --> 01:00:50,680 FULLNESS TO HARD FULLNESS AND 1179 01:00:50,680 --> 01:00:56,160 EVEN TO A STATE OF VERY 1180 01:00:56,160 --> 01:01:06,680 UNCOMFORTABLE SENSATION OR THE 1181 01:01:09,360 --> 01:01:11,360 CEASE SESSION ARE ARRIVING FROM 1182 01:01:11,360 --> 01:01:12,320 THE BLADDER ARE CONVEYED FROM 1183 01:01:12,320 --> 01:01:20,800 THE SPINAL SYSTEM. 1184 01:01:20,800 --> 01:01:23,640 IT'S A SPINAL CORD FROM THERE 1185 01:01:23,640 --> 01:01:27,480 VIA THE SPINAL CORD IT REACHES 1186 01:01:27,480 --> 01:01:32,520 THE BRAIN AND PRESUMABLY 1187 01:01:32,520 --> 01:01:34,920 CORTICAL CENTERS THAT WOULD GIVE 1188 01:01:34,920 --> 01:01:36,560 ACCESS TO CONSCIOUSNESS THAT 1189 01:01:36,560 --> 01:01:41,640 WOULD GIVE ACCESS TO THE 1190 01:01:41,640 --> 01:01:43,560 SENSATIONS AND IN TERMS OF 1191 01:01:43,560 --> 01:01:45,160 CONSCIOUS PERCEPTION. 1192 01:01:45,160 --> 01:01:47,880 SO, A SIMILAR CASE, I BELIEVE, 1193 01:01:47,880 --> 01:01:55,560 MAY BE MADE FOR THE STOMACH, THE 1194 01:01:55,560 --> 01:02:01,160 STOMACH AND THEY ARE CONVEYED 1195 01:02:01,160 --> 01:02:05,080 THROUGH THE SPINAL CORD TO EQUAL 1196 01:02:05,080 --> 01:02:11,120 OR EQUIVALENT CORTICAL CENTERS 1197 01:02:11,120 --> 01:02:21,640 LIKE THESE CORTEX TO FULLNESS 1198 01:02:28,800 --> 01:02:29,080 AND DISCOMFORT. 1199 01:02:29,080 --> 01:02:32,560 MANY OF THE SENSATIONS, 1200 01:02:32,560 --> 01:02:34,240 ESPECIALLY SENSATIONS THAT WE 1201 01:02:34,240 --> 01:02:37,960 ATTRIBUTE TO THE VAGUS NERVE ARE 1202 01:02:37,960 --> 01:02:40,080 ACTUALLY MEDIATED BY SENSORY 1203 01:02:40,080 --> 01:02:43,720 GANGLIA AND SENSORY SPINAL 1204 01:02:43,720 --> 01:02:45,160 GANGLIA. 1205 01:02:45,160 --> 01:02:48,680 SO, WE HAVE BEEN PERFORMING SOME 1206 01:02:48,680 --> 01:02:50,720 ATOMICAL STUDIES THAT ARE 1207 01:02:50,720 --> 01:02:53,000 EQUIVALENT TO WHAT WE HAVE 1208 01:02:53,000 --> 01:02:55,520 PERFORMED FOR THE VEGAS SYSTEM 1209 01:02:55,520 --> 01:02:59,800 AND IN ORDER TO ACHIEVE A ORGAN, 1210 01:02:59,800 --> 01:03:03,520 A SPECIFIC MAPPING OF THE SPINAL 1211 01:03:03,520 --> 01:03:10,040 INNERRIZATINTERINVESTIGATION ANE 1212 01:03:10,040 --> 01:03:11,480 ORGAN OF INTEREST IN THIS CASE 1213 01:03:11,480 --> 01:03:17,440 THE STOMACH AND THE VIRUS STRAIN 1214 01:03:17,440 --> 01:03:22,800 THAT IS RETROGRADE AND CARRIES 1215 01:03:22,800 --> 01:03:27,280 AND THIS WILL RETROGRADE AND GO 1216 01:03:27,280 --> 01:03:29,920 BACKWARDS TO ALL NEURONS 1217 01:03:29,920 --> 01:03:32,760 INNOVATING THE STOMACH AND WE 1218 01:03:32,760 --> 01:03:35,240 PERFORM A SECOND INJECTION 1219 01:03:35,240 --> 01:03:39,040 DIRECTLY IN THE GANGLIA OF A PRE 1220 01:03:39,040 --> 01:03:42,800 DEPEND APARTMENT VIRUS THAT IS 1221 01:03:42,800 --> 01:03:44,240 ON THEY ARE OWE GRADE SO THE 1222 01:03:44,240 --> 01:03:49,080 IDEA HERE IS THAT WE USE THE 1223 01:03:49,080 --> 01:03:50,680 DORRAL ROUTE GANGLIA CELLS THAT 1224 01:03:50,680 --> 01:03:53,160 INNOVATE THE STOMACH AS IT 1225 01:03:53,160 --> 01:03:55,760 STARTER CELLS TO MAP THE GUT 1226 01:03:55,760 --> 01:03:58,280 BRAIN SPINAL PATHWAYS. 1227 01:03:58,280 --> 01:04:01,680 AND IN OUR STUDIES, WE SEE AS 1228 01:04:01,680 --> 01:04:09,080 EXPECTED, LABELING OF DORRAL 1229 01:04:09,080 --> 01:04:12,640 ROUTE GANG GANGLIA AT THE SPINAL 1230 01:04:12,640 --> 01:04:14,120 CODE SO THE VIRUS STARTS 1231 01:04:14,120 --> 01:04:19,040 SPREADING TO THE SPINAL CORD AND 1232 01:04:19,040 --> 01:04:26,040 ESPECIALLY ON LAYER 10 WITH VIS 1233 01:04:26,040 --> 01:04:31,760 ESHAL SEC SESSION AND IT HAS THE 1234 01:04:31,760 --> 01:04:37,000 NUCLEUS THAT IS ASSOCIATED WITH 1235 01:04:37,000 --> 01:04:40,520 SENSATIONS LINKED TO 1236 01:04:40,520 --> 01:04:42,320 TRANSMISSION OF OF THE MUSS LIEU 1237 01:04:42,320 --> 01:04:44,880 CAR SYSTEM VIA THE SPINAL CORD 1238 01:04:44,880 --> 01:04:49,200 SO HERE WE HAVE A PROPER PEW 1239 01:04:49,200 --> 01:04:51,280 KULAR TYPE OF BRAIN CENTER 1240 01:04:51,280 --> 01:04:53,480 APPARENTLY ALSO MEDIATING 1241 01:04:53,480 --> 01:05:04,040 SENSATIONS FROM INTERNAL ORGANS. 1242 01:05:04,560 --> 01:05:07,080 THIS IS INTERESTING THAT FROM 1243 01:05:07,080 --> 01:05:09,400 THE HOUR IN THERE'S LABELING OF 1244 01:05:09,400 --> 01:05:13,040 THE PARA SYMPATHETIC NEURONS OF 1245 01:05:13,040 --> 01:05:17,840 THE VAGUS COMPLEX BUT ALSO NO 1246 01:05:17,840 --> 01:05:21,800 LABELING OF THE VAGAL TARGETS IN 1247 01:05:21,800 --> 01:05:23,800 THE KNEE CLUE US OF THE SOLITARY 1248 01:05:23,800 --> 01:05:25,200 TRACT PROPER SHOWING THAT THE 1249 01:05:25,200 --> 01:05:28,640 SPINAL PATHWAYS IS TO A GREAT 1250 01:05:28,640 --> 01:05:30,640 EXTENT, SEPARATING FROM THE 1251 01:05:30,640 --> 01:05:33,720 VAGAL PATHWAY EVEN THOUGH THEY 1252 01:05:33,720 --> 01:05:36,080 MAY CONVERGE LATER ON IN CERTAIN 1253 01:05:36,080 --> 01:05:42,800 AREAS OF THE HYPOTHALIMUS FOR 1254 01:05:42,800 --> 01:05:43,600 EXAMPLE. 1255 01:05:43,600 --> 01:05:45,000 SO TO START GROBEING ON THE 1256 01:05:45,000 --> 01:05:46,320 FUNCTIONALITY OF THIS SYSTEM 1257 01:05:46,320 --> 01:05:51,280 WE'VE BEEN LOOKING OF THE 1258 01:05:51,280 --> 01:06:01,800 ACTIVITY AND A LOT OF INVE OWE 1259 01:06:12,040 --> 01:06:13,440 AND THESE HAVE FIXED WAKE 1260 01:06:13,440 --> 01:06:17,800 ANIMALS AND WE CHOSE TO USING 1261 01:06:17,800 --> 01:06:18,920 SINGLE CELL RECORDING IN ORDER 1262 01:06:18,920 --> 01:06:22,760 TO ACHIEVE THE SAME TYPE OF 1263 01:06:22,760 --> 01:06:27,400 TEMPORAL RESOLUTIONS AS THE 1264 01:06:27,400 --> 01:06:35,520 ELECTRICITY MIO GRAMS AND A 1265 01:06:35,520 --> 01:06:37,440 LARGE AMOUNT OF UNITS IN THE 1266 01:06:37,440 --> 01:06:41,160 NUCLEUS SEEMS TO BE VERY 1267 01:06:41,160 --> 01:06:43,200 RESPONSIVE TO CHANGES IN GASTRIC 1268 01:06:43,200 --> 01:06:46,360 MOW TILL TEE SO WE SEE MANY 1269 01:06:46,360 --> 01:06:50,560 UNITS BEING EITHER INHIBITED OR 1270 01:06:50,560 --> 01:06:54,040 EXCITED UPON DETECTION OF 1271 01:06:54,040 --> 01:06:58,120 CONTRACTIONS ELICITED BIT 1272 01:06:58,120 --> 01:07:01,640 INFLATION OF THE STOMACH OF THE 1273 01:07:01,640 --> 01:07:03,200 ANIMALS IN SUCH A WAY THAT MANY 1274 01:07:03,200 --> 01:07:06,800 OF THESE UNITS, FOR EXAMPLE, 1275 01:07:06,800 --> 01:07:10,240 THEY MAY BE IN SYNCHRONY WITH 1276 01:07:10,240 --> 01:07:11,920 THE EVENTS OBSERVED IN THE 1277 01:07:11,920 --> 01:07:14,120 STOMACH AND MANY OF THEM ARE 1278 01:07:14,120 --> 01:07:17,160 ACTUALLY INHIBITED AND IT'S 1279 01:07:17,160 --> 01:07:18,600 CONSISTENT WITH THE LITERATURE 1280 01:07:18,600 --> 01:07:25,760 ON OUR UNITS AND RESPONDING TO 1281 01:07:25,760 --> 01:07:26,760 PRO ACCEPTIVE CUES AND THE 1282 01:07:26,760 --> 01:07:30,920 NUMBER OF KUNITZ HAVE BEEN FOUND 1283 01:07:30,920 --> 01:07:35,480 TO BE RESPONSIVE TO EVENTS 1284 01:07:35,480 --> 01:07:37,280 LOCALIZED THIS SHE THOM AK AND 1285 01:07:37,280 --> 01:07:40,600 THE VERY BRIEFLY, I WILL JUST 1286 01:07:40,600 --> 01:07:42,320 DESCRIBE ONE EXPERIMENT WHERE WE 1287 01:07:42,320 --> 01:07:44,480 LOCKED AT IN BEHAVING ANIMALS, 1288 01:07:44,480 --> 01:07:47,920 WE LOOKED AT THE FUNCTIONAL ROLE 1289 01:07:47,920 --> 01:07:52,280 OF THE DRGs INNOVATING THE 1290 01:07:52,280 --> 01:07:57,120 STOMACH SO IN THIS CASE, WE USED 1291 01:07:57,120 --> 01:08:00,560 MICE ON THE IDTR BACKGROUND 1292 01:08:00,560 --> 01:08:03,640 MEANING THEY'VE CONTINUALLY 1293 01:08:03,640 --> 01:08:05,400 EXPRESSED THE TOXIN RECEPTORS 1294 01:08:05,400 --> 01:08:07,640 AND IT'S NOT NORMALLY EXPRESSED 1295 01:08:07,640 --> 01:08:16,360 IN MICE AND SO WE HAVE AGAIN 1296 01:08:16,360 --> 01:08:17,840 INJECTED IT TO THE STOMACH AND 1297 01:08:17,840 --> 01:08:20,760 IT TRAVELED BACK TO THE DORRAL 1298 01:08:20,760 --> 01:08:24,080 ROUTE GANGLIAL AND THE VAGAL 1299 01:08:24,080 --> 01:08:26,800 GANGLIA AND WE A SUPPLIED A 1300 01:08:26,800 --> 01:08:30,240 SALINE INJECTION, WHAT WE SEE IS 1301 01:08:30,240 --> 01:08:34,040 UPON INFLATING A BALLOON ON THE 1302 01:08:34,040 --> 01:08:36,440 STOMACH, WE SEE AS EXPECTED A 1303 01:08:36,440 --> 01:08:39,720 DRASTIC REDUCTION IN FOOD 1304 01:08:39,720 --> 01:08:44,040 INTAKE, HOWEVER, WHEN WE INJECT 1305 01:08:44,040 --> 01:08:45,680 INSTEAD THE TOXIN ITSELF WHICH 1306 01:08:45,680 --> 01:08:48,280 IS GOING TO CUE ONLY CREE 1307 01:08:48,280 --> 01:08:50,440 EXPRESSING NEURONS, DUE TO THE 1308 01:08:50,440 --> 01:08:52,520 BACKGROUND OF THE ANIMAL, WHAT 1309 01:08:52,520 --> 01:08:57,000 WE SEE IS THAT THERE'S A GREAT A 1310 01:08:57,000 --> 01:09:02,000 TIN TEN YOUATION MEANING THE DOL 1311 01:09:02,000 --> 01:09:03,560 ROUTE GANGLIA SEEMS TO BE 1312 01:09:03,560 --> 01:09:06,320 IMPORTANT FOR MEDIATING THE 1313 01:09:06,320 --> 01:09:09,720 SUPPRESSION OF APPETITE AT LEAST 1314 01:09:09,720 --> 01:09:15,000 BY THE PERCEPTION OF AN INFLATED 1315 01:09:15,000 --> 01:09:15,840 STOMACH. 1316 01:09:15,840 --> 01:09:18,280 AND WHEN WE REPEATED THESE 1317 01:09:18,280 --> 01:09:21,040 EXPERIMENTS, EXACTLY THE SAME 1318 01:09:21,040 --> 01:09:25,320 WAY, ALTHOUGH THIS TIME, 1319 01:09:25,320 --> 01:09:27,920 PERFORMING THE LESIONS INTO THE 1320 01:09:27,920 --> 01:09:30,560 VAGAL SENSORY GAGLY A AND THE 1321 01:09:30,560 --> 01:09:33,400 NO-DOSE GANGLIA WE SEE UPON 1322 01:09:33,400 --> 01:09:35,960 INFLATING THE BALLOON, WE SEE 1323 01:09:35,960 --> 01:09:39,160 AGAIN THE DRASTIC REDUCTION IN 1324 01:09:39,160 --> 01:09:43,920 FOOD INSTAKE AFTER SALINE 1325 01:09:43,920 --> 01:09:44,640 INFUSION, HOWEVER. 1326 01:09:44,640 --> 01:09:46,720 WHETHER IT'S INJECTED IN THE 1327 01:09:46,720 --> 01:09:52,080 NO-DOSE GANGLIA WE DID NOT SIGH 1328 01:09:52,080 --> 01:09:54,120 FIFTH CLEAR OF THE EFFECT OF THE 1329 01:09:54,120 --> 01:09:56,520 BALLOON AND MEANING THAT IN 1330 01:09:56,520 --> 01:09:58,880 PRINCIPLE, THE SUPPRESSION OF 1331 01:09:58,880 --> 01:10:01,720 APPETITE CAUSED BY THE 1332 01:10:01,720 --> 01:10:03,960 PERCEPTION OF A BLOATED STOMACH 1333 01:10:03,960 --> 01:10:09,840 IS MUCH MORE HEAVILY DEPENDENT 1334 01:10:09,840 --> 01:10:12,040 ON A SPINAL TRANCE WAY 1335 01:10:12,040 --> 01:10:13,600 TRANSMITTING FROM THE STOMACH TO 1336 01:10:13,600 --> 01:10:15,160 THE BRAIN THEY GO PATHWAYS. 1337 01:10:15,160 --> 01:10:17,480 THE VAGUS IS GOING TO PERFORM A 1338 01:10:17,480 --> 01:10:20,880 NUMBER OF OTHER FUNCTIONS 1339 01:10:20,880 --> 01:10:21,800 PROBABLY SECRETARY FUNCTIONS 1340 01:10:21,800 --> 01:10:25,600 LIKE ACID RELEASE UPON GASTRIC 1341 01:10:25,600 --> 01:10:28,360 DISTINCTION BUT THIS BEHAVIORAL 1342 01:10:28,360 --> 01:10:30,520 READ OUT DOES NOT SEEM TO BE 1343 01:10:30,520 --> 01:10:34,440 HEAVILY DEPENDENT ON THE VAGUS 1344 01:10:34,440 --> 01:10:34,920 NERVE. 1345 01:10:34,920 --> 01:10:38,360 SO, TO SUMMARIZE, OUR TRACING 1346 01:10:38,360 --> 01:10:40,320 AND FUNCTION OF THE STUDIES 1347 01:10:40,320 --> 01:10:43,080 SEEMS TO SUGGEST THAT DORRAL 1348 01:10:43,080 --> 01:10:45,600 ROUTE GANGLIA AND THE SPINAL 1349 01:10:45,600 --> 01:10:50,000 SYSTEMS THEY DETECT INFORMATION 1350 01:10:50,000 --> 01:10:53,480 OF OCCURRING IN THE STOMACH AT 1351 01:10:53,480 --> 01:10:56,200 THE LEAST MECHANISM CESSATION 1352 01:10:56,200 --> 01:10:59,080 AND MEET THAT INFORMATION TO 1353 01:10:59,080 --> 01:11:01,680 LOWER CENTERS IN THE BRAIN STEM 1354 01:11:01,680 --> 01:11:02,920 AND FROM THERE THIS IS SOMETHING 1355 01:11:02,920 --> 01:11:05,640 THAT WE ARE INTERESTED IN ALSO 1356 01:11:05,640 --> 01:11:09,160 AND WE ALSO SOME LOCALIZED BUT 1357 01:11:09,160 --> 01:11:11,680 INTERESTING LABELING IN SOME 1358 01:11:11,680 --> 01:11:14,840 PARTS OF THE SOMATO SENSORY 1359 01:11:14,840 --> 01:11:16,240 CONTEXT KNOWN TO MEDIATE 1360 01:11:16,240 --> 01:11:19,800 CONSCIOUS PERCEPTIONS OF BODY 1361 01:11:19,800 --> 01:11:21,800 PARTS IN AT LEAST IN TERMS OF 1362 01:11:21,800 --> 01:11:28,880 THE MUSCULAR SYSTEM. 1363 01:11:28,880 --> 01:11:34,600 SO IN OVER ALL, WE BELIEVE THAT 1364 01:11:34,600 --> 01:11:37,840 THE IT MAY CONTRIBUTE TO THIS 1365 01:11:37,840 --> 01:11:42,600 MORE GENERAL SENSATION AND IT 1366 01:11:42,600 --> 01:11:45,720 MAY HELP THE BRYN TO PERFORM 1367 01:11:45,720 --> 01:11:47,960 COMMUTATIONS LIKE POSITIONING IN 1368 01:11:47,960 --> 01:11:49,800 SPACE AND YOUR ORIENTATION OF 1369 01:11:49,800 --> 01:11:52,160 THE BODY SINCE OUR INTERNAL 1370 01:11:52,160 --> 01:11:53,320 ORGANS, FOR EXAMPLE, THEY 1371 01:11:53,320 --> 01:11:55,600 STOMACH AND THE BLADDER, ACCESS 1372 01:11:55,600 --> 01:12:00,440 TO CONSCIOUSNESS AND PERFORM OR 1373 01:12:00,440 --> 01:12:02,080 PROVIDE SOME CUE IN TERMS OF 1374 01:12:02,080 --> 01:12:05,880 WHERE WE ARE IN SPACE AND HOW 1375 01:12:05,880 --> 01:12:08,360 OUR BODIES ARE ORIENTED. 1376 01:12:08,360 --> 01:12:13,520 AND I WOULD LIKE TO END BY 1377 01:12:13,520 --> 01:12:17,560 THANKING MY COLLEAGUES WHO DID 1378 01:12:17,560 --> 01:12:19,160 ALL THIS WORK ESPECIALLY THE 1379 01:12:19,160 --> 01:12:21,560 SURGICAL AND FUNCTIONAL APPROACH 1380 01:12:21,560 --> 01:12:24,600 AND MATTHEW WHO IS DOING GREAT 1381 01:12:24,600 --> 01:12:29,200 WORK ON ELECTRIC PHYSIOLOGY AND 1382 01:12:29,200 --> 01:12:29,680 THANK YOU. 1383 01:12:29,680 --> 01:12:33,240 [APPLAUSE] 1384 01:12:33,240 --> 01:12:36,680 THANK YOU, WHILE THE NEXT 1385 01:12:36,680 --> 01:12:41,080 SPEAKER Dr. OKA IS COMING UP, 1386 01:12:41,080 --> 01:12:42,240 WE'LL HAVE ROM FOR QUESTIONS. 1387 01:12:42,240 --> 01:12:44,240 ANYONE HAVE A QUESTION HERE? 1388 01:12:44,240 --> 01:12:49,720 WE HAVE SOMETHING IN THE CHAT? 1389 01:12:49,720 --> 01:12:50,680 IT'S VERY INTERESTING AND MY 1390 01:12:50,680 --> 01:12:52,240 QUESTION IS THAT WHICH PRESSURE 1391 01:12:52,240 --> 01:12:55,520 DID YOU USE WHEN YOU DISTEND THE 1392 01:12:55,520 --> 01:12:55,880 STOMACH? 1393 01:12:55,880 --> 01:12:57,440 >>WHICH PRESSURE? 1394 01:12:57,440 --> 01:12:57,680 >>YEAH. 1395 01:12:57,680 --> 01:13:01,640 >>WELL I MEAN -- WE TRIED A 1396 01:13:01,640 --> 01:13:03,320 RANGE OF PRESSURES. 1397 01:13:03,320 --> 01:13:05,920 SO IT'S A LITTLE COMPLICATED 1398 01:13:05,920 --> 01:13:07,440 BECAUSE I CAN EXPLAIN TO YOU 1399 01:13:07,440 --> 01:13:10,960 LATER BUT BASICALLY WE 1400 01:13:10,960 --> 01:13:13,840 DETERMINED IT BY BEHAVIORAL 1401 01:13:13,840 --> 01:13:20,240 ASIZATIOAASSAYS SO WE LOCKED ATH 1402 01:13:20,240 --> 01:13:22,840 PRESSURE THE BALLOON WOULD 1403 01:13:22,840 --> 01:13:25,000 PREVENT FURTHER FOOD INTAKE IN A 1404 01:13:25,000 --> 01:13:27,960 PARTICULAR ANIMAL AND WE 1405 01:13:27,960 --> 01:13:29,880 REAPPLIED THAT DURING THE 1406 01:13:29,880 --> 01:13:31,000 BEHAVIORAL ASSAY. 1407 01:13:31,000 --> 01:13:33,760 >>THE REASON I'M ASKING IS THE 1408 01:13:33,760 --> 01:13:35,640 PATHWAY IS DEPENDENT ON THE 1409 01:13:35,640 --> 01:13:39,200 PRESSURE OF FOOD ATTENTION SO 1410 01:13:39,200 --> 01:13:43,880 PROBLEM VAGUS IS MORE INVOLVED 1411 01:13:43,880 --> 01:13:46,480 BUT IF IT'S GOES THROUGH THE 1412 01:13:46,480 --> 01:13:47,520 SYMPATHETIC PATHWAY LIKE YOU 1413 01:13:47,520 --> 01:13:47,800 REPORTED. 1414 01:13:47,800 --> 01:13:48,840 >>YEAH, THAT'S RIGHT. 1415 01:13:48,840 --> 01:13:51,360 I MEAN, YEAH, EXACTLY. 1416 01:13:51,360 --> 01:13:55,960 WE COULD LOOK AT THE POSSIBILITY 1417 01:13:55,960 --> 01:13:56,960 FOR OUR NAUSEA OR PAIN AND WE 1418 01:13:56,960 --> 01:14:00,160 DID A NUMBER OF BEHAVIORAL ASSAY 1419 01:14:00,160 --> 01:14:02,360 I DON'T HAVE THE TIME TO EXPLAIN 1420 01:14:02,360 --> 01:14:04,480 TO VERIFY THAT THE ANIMALS ARE 1421 01:14:04,480 --> 01:14:06,000 PERFORMING OTHER FUNCTIONS 1422 01:14:06,000 --> 01:14:06,280 NORMALLY. 1423 01:14:06,280 --> 01:14:07,960 THEY ARE JUST NOT INTERESTED IN 1424 01:14:07,960 --> 01:14:09,640 FOOD, YEAH. 1425 01:14:09,640 --> 01:14:11,640 BUT THAT'S A GOOD POINT. 1426 01:14:11,640 --> 01:14:13,200 >>THAT'S A GREAT QUESTION TO 1427 01:14:13,200 --> 01:14:15,320 CONTINUE AT THE END. 1428 01:14:15,320 --> 01:14:25,680 SO, PLEASE GO AHEAD. 1429 01:14:40,040 --> 01:14:41,000 >>GREAT, YEAH. 1430 01:14:41,000 --> 01:14:42,360 THANK YOU SO MUCH FOR IN 1431 01:14:42,360 --> 01:14:45,760 INVITING ME AND I'M VERY HAPPY 1432 01:14:45,760 --> 01:14:47,760 TO SHARE OUR RECENT RESULTS. 1433 01:14:47,760 --> 01:14:55,480 I'M GOING TO TALK ABOUT THE 1434 01:14:55,480 --> 01:14:56,680 GUT-TO-BRAIN NEUROCIRCUIT. 1435 01:14:56,680 --> 01:14:58,720 FOR THE MAIN FOCUS OF OUR 1436 01:14:58,720 --> 01:15:00,920 LABORATORY IS TO UNDERSTAND HOW 1437 01:15:00,920 --> 01:15:01,520 THE WHOLE BOD OH NOT JUST THE 1438 01:15:01,520 --> 01:15:04,560 BRAIN BUT THE GUT AND BRAIN, 1439 01:15:04,560 --> 01:15:06,720 REGULATES THE INTERNAL FLUID 1440 01:15:06,720 --> 01:15:10,040 BALANCE SO THE FLUID BALANCE IS 1441 01:15:10,040 --> 01:15:11,680 REALLY BALANCED BY TWO CO 1442 01:15:11,680 --> 01:15:13,240 FACTORS, ONE IS WATER AND TO THE 1443 01:15:13,240 --> 01:15:17,960 LEFT AND ONE IS SODIUM. 1444 01:15:17,960 --> 01:15:19,760 SO UNLIKE FOOD OR HUNGER, WHICH 1445 01:15:19,760 --> 01:15:22,520 HAS A LOT OF COMPONENTS, SUGAR, 1446 01:15:22,520 --> 01:15:25,920 FAT AND PROTEIN, THESE TWO PURE 1447 01:15:25,920 --> 01:15:27,840 COMPONENTS, WATER AND SODIUM, IS 1448 01:15:27,840 --> 01:15:31,000 REALLY IMPORTANT FOR OUR BODIES 1449 01:15:31,000 --> 01:15:35,040 FLUID BALANCE AND IT'S NOT JUST 1450 01:15:35,040 --> 01:15:37,000 EATING A LOT, SO PROBABLE 1451 01:15:37,000 --> 01:15:38,520 BECAUSE IF YOU EAT A LOT OF 1452 01:15:38,520 --> 01:15:40,360 SODIUM, EVEN IF YOU NEED IT, IT 1453 01:15:40,360 --> 01:15:42,520 WILL MAKE YOU HYPERTENSION AND 1454 01:15:42,520 --> 01:15:44,880 SO YOU NEED TO HAVE APPROPRIATE 1455 01:15:44,880 --> 01:15:48,600 AMOUNT AND HAVE TO GET THE 1456 01:15:48,600 --> 01:15:50,720 SPECIFIC FACTOR TO MAINTAIN THE 1457 01:15:50,720 --> 01:15:53,760 BALANCE AND THEN LIKE I SAID, 1458 01:15:53,760 --> 01:15:57,080 IT'S NOT JUST THE BRAIN, IT 1459 01:15:57,080 --> 01:15:58,640 TURNED OUT THAT THE REGULATION 1460 01:15:58,640 --> 01:16:01,000 OF INTAKE OF WATER AND SODIUM 1461 01:16:01,000 --> 01:16:02,920 HAS A LOT OF MODULATION FROM THE 1462 01:16:02,920 --> 01:16:04,280 GUT AND THE BODY RIGHT. 1463 01:16:04,280 --> 01:16:07,640 THE ONE EXAMPLE IS A SENSE TOM 1464 01:16:07,640 --> 01:16:11,800 LIKE AND ALSO SOME SENSATION IN 1465 01:16:11,800 --> 01:16:15,720 THE SWALLOWING STUFF AND THEN 1466 01:16:15,720 --> 01:16:17,240 ALSO GUT SENSATION AFTER EATING 1467 01:16:17,240 --> 01:16:20,320 AND DRINKING. 1468 01:16:20,320 --> 01:16:22,840 SO, AND THEN FOR THIRST THE 1469 01:16:22,840 --> 01:16:24,760 REGULATION IN THE BRAIN SO THE 1470 01:16:24,760 --> 01:16:32,280 MAIN STRUCTURE THAT REGULATES 1471 01:16:32,280 --> 01:16:35,600 THIRST IS A THIN LAYER STRUCTURE 1472 01:16:35,600 --> 01:16:42,080 THAT HAS THREE NEWLY EYE AND THE 1473 01:16:42,080 --> 01:16:46,880 SENSORY OF AND EXPOSED TO THE 1474 01:16:46,880 --> 01:16:49,480 BLOOD AND AND P.O. IS 1475 01:16:49,480 --> 01:16:52,760 INCOMPETENT GREAT TIVE NUCLEUS 1476 01:16:52,760 --> 01:16:53,680 SENSITIVE INFORMATION FROM AND 1477 01:16:53,680 --> 01:16:54,840 CENTS THE INFORMATION BACK TO 1478 01:16:54,840 --> 01:17:05,240 THE REST OF THE BRAIN. 1479 01:17:07,120 --> 01:17:08,760 WHEN YOU LOSE VOLUME IN THE 1480 01:17:08,760 --> 01:17:12,480 BLOOD OR THE CHANGE AND THAT 1481 01:17:12,480 --> 01:17:16,600 ACTIVATES SPECIFIC TYPE OF 1482 01:17:16,600 --> 01:17:19,120 NEURONS AND STIMULATION WITH 1483 01:17:19,120 --> 01:17:22,880 SOME ACTIVATION TOOLS AND I CAN 1484 01:17:22,880 --> 01:17:25,280 SHOW YOU IN THIS CASE -- I CAN'T 1485 01:17:25,280 --> 01:17:31,120 SHOW YOU THE VIDEO UNFORTUNATELY 1486 01:17:31,120 --> 01:17:32,320 BUT IT'S LINKED TO 1487 01:17:32,320 --> 01:17:35,160 THE BEHAVIOR BECAUSE YOU CAN 1488 01:17:35,160 --> 01:17:36,680 IMMEDIATELY DRY THE FEELING AND 1489 01:17:36,680 --> 01:17:40,240 WE SEE IT IN ONE SECOND. 1490 01:17:40,240 --> 01:17:41,720 AND ININCLUDEDDING MY LABORATORY 1491 01:17:41,720 --> 01:17:44,720 AND MANY OTHER LABORATORY, WE 1492 01:17:44,720 --> 01:17:47,120 FOUND THAT THIS INTRA ACCEPTIVE 1493 01:17:47,120 --> 01:17:49,560 NEURONS THAT ARE A BRAIN SENSOR 1494 01:17:49,560 --> 01:17:51,560 NEURONS, NOT JUST MONITOR OUR 1495 01:17:51,560 --> 01:17:54,640 INTERNAL BODY STATE BUT MONITOR 1496 01:17:54,640 --> 01:17:56,840 REALLY SORT OF OUR BEHAVIOR 1497 01:17:56,840 --> 01:18:05,840 STATE OR NUTRIENT REPLENISH FROM 1498 01:18:05,840 --> 01:18:07,280 THE GUT TO THE BRAIN. 1499 01:18:07,280 --> 01:18:10,720 SO ALSO, INTERESTING ABOUT IT, 1500 01:18:10,720 --> 01:18:13,960 THE DIFFERENT MUTANT FACT LIKE 1501 01:18:13,960 --> 01:18:16,440 WATER RAPIDS AND FOOD AND THESE 1502 01:18:16,440 --> 01:18:18,240 RECEIVE DIFFERENT TYPE OF 1503 01:18:18,240 --> 01:18:22,360 SENSORY FEEDBACK AND IN THE CASE 1504 01:18:22,360 --> 01:18:26,400 GULPING AND OSMOLAITY AND IN 1505 01:18:26,400 --> 01:18:28,720 HUNGER CASE AND TASTE SMELL, 1506 01:18:28,720 --> 01:18:36,000 SIGHT OR C OR CALORIC VALUE ANDE 1507 01:18:36,000 --> 01:18:38,560 ACTIVITY OF THE INTER ACCEPT 1508 01:18:38,560 --> 01:18:41,960 NEURONS BEFORE DIFFERENT TIMES 1509 01:18:41,960 --> 01:18:44,200 OF NUTRIENT FACTOR. 1510 01:18:44,200 --> 01:18:51,120 SO WE FOCUSED ON THE SENSING AND 1511 01:18:51,120 --> 01:18:54,320 HOW THAT SIGNAL, YOU KNOW, GIVES 1512 01:18:54,320 --> 01:18:56,560 MODULATION TO THE BRAIN AND WHEN 1513 01:18:56,560 --> 01:18:58,440 YOU DRINK WATER, YOU DRINK WATER 1514 01:18:58,440 --> 01:19:02,200 GETS TO THE STOMACH HERE AND IT 1515 01:19:02,200 --> 01:19:05,800 GOES THROUGH THE INTESTINE AND 1516 01:19:05,800 --> 01:19:08,400 IT'S ABSORBED THROUGH THE LARGE 1517 01:19:08,400 --> 01:19:10,000 VESSEL CALLED THE PORTAL VEIN 1518 01:19:10,000 --> 01:19:12,360 AND THAT IS WATER GOES THROUGH 1519 01:19:12,360 --> 01:19:13,840 THE CIRCULATION. 1520 01:19:13,840 --> 01:19:16,840 SO IN THESE ORGANS, ARE 1521 01:19:16,840 --> 01:19:20,360 INNOVATED BY TWO DISTINCT 1522 01:19:20,360 --> 01:19:22,840 SYSTEMS LIKE ONE IS THE SPINAL 1523 01:19:22,840 --> 01:19:27,720 PATHWAY AND ANOTHER ONE IS A 1524 01:19:27,720 --> 01:19:29,640 VAGAL PATHWAY SO WE LOOKED FOR 1525 01:19:29,640 --> 01:19:32,080 THE POSSIBILITY AND HOW THEY 1526 01:19:32,080 --> 01:19:33,160 RESPOND THROUGH CHANGE THE GUARD 1527 01:19:33,160 --> 01:19:35,160 AND FOR THE FIRST ONE WE LOOKED 1528 01:19:35,160 --> 01:19:45,600 AT THE DRG PATHWAY AND THE 1529 01:19:59,200 --> 01:20:00,320 CONTROL OF THE SKIN PINCH 1530 01:20:00,320 --> 01:20:04,360 BECAUSE IT'S SENSITIVE TO 1531 01:20:04,360 --> 01:20:06,360 (INAUDIBLE) SO WE FOUND THAT FEW 1532 01:20:06,360 --> 01:20:07,760 POPULATION OF DRG NEURONS 1533 01:20:07,760 --> 01:20:09,440 RESPONSE TO ANY NUTRIENT FACTORS 1534 01:20:09,440 --> 01:20:12,240 IN THEN ADVERTISE TIN LIKE 1535 01:20:12,240 --> 01:20:13,280 WATER, SODIUM, AND THEY 1536 01:20:13,280 --> 01:20:20,160 RESPONDED BUT IT'S NOT VERY TIME 1537 01:20:20,160 --> 01:20:20,400 LOCKED. 1538 01:20:20,400 --> 01:20:24,280 SO WE LOOKED INTO THE ANOTHER 1539 01:20:24,280 --> 01:20:26,280 SUBSYSTEMS WHICH IS THE VAGUS 1540 01:20:26,280 --> 01:20:29,880 SYSTEM AND WE STARTED TO RECORD 1541 01:20:29,880 --> 01:20:31,960 THE NERVE ACTIVITY FROM THE 1542 01:20:31,960 --> 01:20:33,680 ENTIRE NERVE AND INTERESTINGLY 1543 01:20:33,680 --> 01:20:35,720 WE FOUND THAT THESE NERVES 1544 01:20:35,720 --> 01:20:39,160 RESPOND VERY STRONGLY TO THE 1545 01:20:39,160 --> 01:20:42,800 HYPO STIMULI IN THE INTESTINE 1546 01:20:42,800 --> 01:20:47,640 AND IN FACT, FROM THE BOTTOM 1547 01:20:47,640 --> 01:20:53,200 BLACK LINE AND IT'S 150 MILL 1548 01:20:53,200 --> 01:20:56,440 MALL AND TO SO THIS IS REALLY 1549 01:20:56,440 --> 01:20:58,800 NOT THE SINGLE CELL RESOLUTION 1550 01:20:58,800 --> 01:21:00,680 AND IF YOU LOCK AT THE SINGLE 1551 01:21:00,680 --> 01:21:03,640 CELL RESOLUTION, AGAIN, IT 1552 01:21:03,640 --> 01:21:05,280 DOESN'T REALLY, YOU KNOW, PLAY 1553 01:21:05,280 --> 01:21:07,560 SO WE HAVE TO TAKE MY WORD. 1554 01:21:07,560 --> 01:21:12,680 SO YOU CAN SEE REALLY SPARSE AND 1555 01:21:12,680 --> 01:21:16,680 STRONG CALCIUM RESPONSES EFFECT 1556 01:21:16,680 --> 01:21:21,520 BY JUST PUTTING WATER INTO THE 1557 01:21:21,520 --> 01:21:25,040 INTESTINE AND SO, AGAIN, THIS IS 1558 01:21:25,040 --> 01:21:26,560 JUST THE WATER RESPONSE BUT IF 1559 01:21:26,560 --> 01:21:29,440 WE NOW TEST DIFFERENTLY LIKE 1560 01:21:29,440 --> 01:21:33,480 WATER AND HIGH SODIUM STIMULUS, 1561 01:21:33,480 --> 01:21:38,280 AND ALSO SUGAR AND WE SAW A 1562 01:21:38,280 --> 01:21:41,360 MOSTLY POPULATION BUT SOME BUT 1563 01:21:41,360 --> 01:21:42,960 POPULATION LIGHT UP AND BY 1564 01:21:42,960 --> 01:21:44,840 DIFFERENT FACTORS. 1565 01:21:44,840 --> 01:21:55,400 SO NOW WE ASK FOR POPULATION AND 1566 01:22:02,520 --> 01:22:05,080 WE FOUND WHO GENETIC LINE WITH A 1567 01:22:05,080 --> 01:22:07,320 CONTRASTING RESPONSE AND ONE IS 1568 01:22:07,320 --> 01:22:13,400 A TAC-1-CRE AI AND STIMULUS AND 1569 01:22:13,400 --> 01:22:17,560 THE OTHER NTS-CRE IS A DIFFERENT 1570 01:22:17,560 --> 01:22:19,400 TYPE OF SEC SET NEURONS AND THEY 1571 01:22:19,400 --> 01:22:20,720 DIDN'T SHOW RESPONSE AND SO IT'S 1572 01:22:20,720 --> 01:22:22,600 JUST A MARKER BUT IT DOESN'T 1573 01:22:22,600 --> 01:22:23,920 REALLY -- IT'S NOT VERY CLEAN 1574 01:22:23,920 --> 01:22:25,920 MARKER BUT IT GAVE ME SORT OF A 1575 01:22:25,920 --> 01:22:27,600 HINT WHERE TO LOOK AT AND SAYING 1576 01:22:27,600 --> 01:22:30,280 THAT WHERE THAT THEY SENSING 1577 01:22:30,280 --> 01:22:33,160 HAPPENS AND SO, THE BIGGEST 1578 01:22:33,160 --> 01:22:36,920 DIFFERENCE WE FOUND AND IS THE 1579 01:22:36,920 --> 01:22:40,240 INNOVATION TO THE TIP ATTIC 1580 01:22:40,240 --> 01:22:42,120 BRAIN AND FOR THE LIVER AREA AND 1581 01:22:42,120 --> 01:22:44,600 AS YOU CAN SEE HERE TO THE 1582 01:22:44,600 --> 01:22:47,720 RIGHT, YOU CAN SEE A STRONG 1583 01:22:47,720 --> 01:22:49,760 LABELING OF INNOVATION IN THE 1584 01:22:49,760 --> 01:22:55,480 VAGAL NEURONS BUT NOT IN THE 1585 01:22:55,480 --> 01:22:55,720 NTS-CRE. 1586 01:22:55,720 --> 01:22:57,800 THIS IS A MOST PROMINENT 1587 01:22:57,800 --> 01:22:58,680 DIFFERENCE. 1588 01:22:58,680 --> 01:23:01,360 WE HIGH POTH A SIZE THAT MAYBE 1589 01:23:01,360 --> 01:23:04,560 THOSE INNOVATION FROM HPA MIGHT 1590 01:23:04,560 --> 01:23:11,520 BE IMPORTANT FOR OS MOW SENSEING 1591 01:23:11,520 --> 01:23:14,200 AND WHEN WE CUT THIS SMALL 1592 01:23:14,200 --> 01:23:17,840 BRANCH TO THE VEIN, HERE, THE 1593 01:23:17,840 --> 01:23:19,160 LEFT SIDE IS WATER RESPONSE 1594 01:23:19,160 --> 01:23:21,160 BEFORE AND THE RIGHT SIDE IS 1595 01:23:21,160 --> 01:23:23,520 AFTER THE INNOVATION AND IT'S 1596 01:23:23,520 --> 01:23:31,800 ALMOST COMPLETELY GONE BUT THE 1597 01:23:31,800 --> 01:23:36,040 TACTICS -- TACTILE DID NOT 1598 01:23:36,040 --> 01:23:37,000 CHANGE. 1599 01:23:37,000 --> 01:23:39,800 THERE'S A LOT OF HYPE TONIC 1600 01:23:39,800 --> 01:23:43,440 RESPONSES AND THEN THE QUESTION 1601 01:23:43,440 --> 01:23:45,680 IS, WE KNOW WHERE TO LOOK AT 1602 01:23:45,680 --> 01:23:47,840 SENSING OR THE RESPONSES BUT THE 1603 01:23:47,840 --> 01:23:49,720 KEY IF WE -- IF THESE RESPONSES 1604 01:23:49,720 --> 01:23:52,120 ARE IMPORTANT FOR REGULATION OF 1605 01:23:52,120 --> 01:23:55,880 THE BRAIN, RIGHT, SO WE COMBINE 1606 01:23:55,880 --> 01:23:59,280 THE OPERATION AND THEN CALCIUM 1607 01:23:59,280 --> 01:24:01,600 RECORDING FROM THE INTEROCEPTION 1608 01:24:01,600 --> 01:24:02,360 NEURONS IN THE BRAIN. 1609 01:24:02,360 --> 01:24:08,640 SO HERE IS THE SFO, WE RECORD IT 1610 01:24:08,640 --> 01:24:10,600 AND AT THE SAME TIME WE OPERATE 1611 01:24:10,600 --> 01:24:13,160 IT IN THE GUT SO THIS GRAPH, THE 1612 01:24:13,160 --> 01:24:17,480 BLACK LINE IS GENERAL NORMAL 1613 01:24:17,480 --> 01:24:19,280 RESPONSE AND BEFORE AND AFTER 1614 01:24:19,280 --> 01:24:19,560 DRINKING. 1615 01:24:19,560 --> 01:24:22,920 SO BEFORE DRINKING, YOU FEEL A 1616 01:24:22,920 --> 01:24:24,560 TIGHT ACTIVITY LEVEL OF CALCIUM 1617 01:24:24,560 --> 01:24:26,240 BUT WHEN YOU START DRINKING 1618 01:24:26,240 --> 01:24:28,920 WATER AND THIS ACTIVITY DROPS 1619 01:24:28,920 --> 01:24:30,360 VERY RAPIDLY. 1620 01:24:30,360 --> 01:24:32,560 AFTER THE INNOVATION OF THIS 1621 01:24:32,560 --> 01:24:36,600 SPECIFIC BRANCH OF THE VEIN, 1622 01:24:36,600 --> 01:24:40,120 THEN, THE SORT OF QUENCHING 1623 01:24:40,120 --> 01:24:45,520 EFFECT THE SUPPRESSION OF THE 1624 01:24:45,520 --> 01:24:50,080 NEURONS IS LARGELY GONE. 1625 01:24:50,080 --> 01:24:51,960 THE IMPORTANT PART AS I SAID, SO 1626 01:24:51,960 --> 01:24:53,680 THERE ARE TWO COMPONENTS. 1627 01:24:53,680 --> 01:24:57,440 ONE IS THE GULPING AND ANOTHER 1628 01:24:57,440 --> 01:24:57,720 (INAUDIBLE). 1629 01:24:57,720 --> 01:24:59,600 THE GOOD CONTROL IS THAT THE 1630 01:24:59,600 --> 01:25:02,360 GULPING PART IS NOT AFFECTED, 1631 01:25:02,360 --> 01:25:03,320 RIGHT. 1632 01:25:03,320 --> 01:25:07,680 SO I NOW IN LARGE SO IF I LOOK 1633 01:25:07,680 --> 01:25:09,080 AT THE INITIAL SEPARATION OF 1634 01:25:09,080 --> 01:25:11,200 THESE NEURONS WHICH IS BEING 1635 01:25:11,200 --> 01:25:13,320 USED BY GULPING IS UNCHANGED, 1636 01:25:13,320 --> 01:25:14,600 RIGHT. 1637 01:25:14,600 --> 01:25:18,160 THE ONLY CHANGE IS THIS 1638 01:25:18,160 --> 01:25:25,120 PROLONGED SEPARATION AND AGAIN 1639 01:25:25,120 --> 01:25:27,360 INDICATES THIS CHANGES 1640 01:25:27,360 --> 01:25:31,680 SEPARATION AND SO FAR, I HAVE 1641 01:25:31,680 --> 01:25:33,320 TALKED ABOUT THE AREA IS 1642 01:25:33,320 --> 01:25:38,640 IMPORTANT FOR TRANSMITTING 1643 01:25:38,640 --> 01:25:40,440 OSMOLAITY TO THE BRAIN BUT ONE 1644 01:25:40,440 --> 01:25:42,360 THING THAT WASN'T CLEAR IS THE 1645 01:25:42,360 --> 01:25:47,960 HPA DIRECTLY SENSING OSMOLALITY 1646 01:25:47,960 --> 01:25:49,280 CHANGE AND DIRECT THREE THROUGH 1647 01:25:49,280 --> 01:25:52,720 SOMETHING ELSE. 1648 01:25:52,720 --> 01:25:54,840 THIS IS ONE OF THE FINDINGS FOR 1649 01:25:54,840 --> 01:25:57,200 US BUT WE TEST THIS AND WE DID 1650 01:25:57,200 --> 01:25:59,680 MORE COMPLICATED SURGERY IN THE 1651 01:25:59,680 --> 01:26:03,680 SAME ANIMAL WE CHANGED THE OS 1652 01:26:03,680 --> 01:26:05,120 MOWALITY IN THE TESTING AND 1653 01:26:05,120 --> 01:26:08,520 CHANGING IT IN THE PORTAL VEIN 1654 01:26:08,520 --> 01:26:10,960 SO WE HAVE TOO MANY TUBES IN THE 1655 01:26:10,960 --> 01:26:13,760 GUT AND THEN WE DID ALL THESE 1656 01:26:13,760 --> 01:26:15,200 EXPERIMENTS SO THIS IS THE 1657 01:26:15,200 --> 01:26:18,040 RESULT HERE. 1658 01:26:18,040 --> 01:26:20,880 WE FIRST INFUSE THE WATER IN THE 1659 01:26:20,880 --> 01:26:22,480 INTESTINE AND YOU GET A LOT OF 1660 01:26:22,480 --> 01:26:23,560 RESPONSE RIGHT. 1661 01:26:23,560 --> 01:26:28,400 WE DILUTED THE BLOOD INTO THE 1662 01:26:28,400 --> 01:26:32,800 HPV SO THERE'S NO RESPONSE OF 1663 01:26:32,800 --> 01:26:33,120 THAT. 1664 01:26:33,120 --> 01:26:35,440 WE EXPECT THIS IS DILUTION OF 1665 01:26:35,440 --> 01:26:38,040 BLOOD BUT IT'S NOT THE CASE AND 1666 01:26:38,040 --> 01:26:41,320 IT'S NOT PER SE IT'S OX SEDATING 1667 01:26:41,320 --> 01:26:45,000 SO NOW WE NOW ASK THE NEXT 1668 01:26:45,000 --> 01:26:45,360 HYPOTHESIS. 1669 01:26:45,360 --> 01:26:47,040 MAYBE THIS IS IS SOMETHING THAT 1670 01:26:47,040 --> 01:26:50,320 SECRETED FROM THE INTESTINE THAT 1671 01:26:50,320 --> 01:26:52,320 ACTIVATES THESE NEURONS. 1672 01:26:52,320 --> 01:26:54,800 THERE ARE MANY PEPTIDES KNOWN TO 1673 01:26:54,800 --> 01:26:58,720 BE SECRETED FROM THE INTESTINE 1674 01:26:58,720 --> 01:27:00,360 BASED ON FOOD AND WATER AND ONE 1675 01:27:00,360 --> 01:27:05,760 OF THEM WAS LIKE V.I.P. AND 1676 01:27:05,760 --> 01:27:09,920 THESE RESPONSE WHEN WE INFUSE 1677 01:27:09,920 --> 01:27:12,440 VIP NO THE VEIN, IT'S NOT LIKE 1678 01:27:12,440 --> 01:27:17,640 PERFECT OVER ALL BUT AT LEAST 1679 01:27:17,640 --> 01:27:28,200 PARTIAL NUMBERS AT LEAST VIP IS 1680 01:27:36,280 --> 01:27:37,440 CONTRIBUTING TO THE RESPONSE OF 1681 01:27:37,440 --> 01:27:41,680 THE OSMOLALITY AND SO, AS 1682 01:27:41,680 --> 01:27:43,560 EXPECTED, ONE OF THE VIP 1683 01:27:43,560 --> 01:27:46,760 RECEPTORS, VIP RECEPTORS TYPE 2 1684 01:27:46,760 --> 01:27:51,800 IS STRONGLY PRESSED IN THE HPA 1685 01:27:51,800 --> 01:27:53,720 AREA AND THEN WHAT OUR RESPONSE 1686 01:27:53,720 --> 01:27:57,600 AND ALSO VIP RESPONSES OF BOTH 1687 01:27:57,600 --> 01:28:00,600 SEPARATE IN THE HIP ATTIC IN VE 1688 01:28:00,600 --> 01:28:03,560 OWE EXPERIMENTS SO FROM THIS 1689 01:28:03,560 --> 01:28:08,040 RESULT NOW, WE CAN NOW CONCLUDE 1690 01:28:08,040 --> 01:28:10,200 AT LEAST SO FARTHER BRAIN HAS A 1691 01:28:10,200 --> 01:28:16,360 LOT OF RAPID MODULATION FROM THE 1692 01:28:16,360 --> 01:28:18,800 GUT AND THEN ONE FACTORS IS THE 1693 01:28:18,800 --> 01:28:20,600 CHANGING THE GUT WHICH IS NOW 1694 01:28:20,600 --> 01:28:23,240 TRANSMITTED THROUGH THE VAGUS 1695 01:28:23,240 --> 01:28:28,000 AND THIS IS NOW THE TRANSLATED 1696 01:28:28,000 --> 01:28:31,960 INTO HORMONAL SITUATION TO 1697 01:28:31,960 --> 01:28:33,040 ACTIVATE THE NEURONS. 1698 01:28:33,040 --> 01:28:34,920 THIS IS CREATING A LOT OF 1699 01:28:34,920 --> 01:28:36,160 DIFFERENT QUESTIONS THAT WE NEED 1700 01:28:36,160 --> 01:28:38,440 TO CHALLENGE SO, LIKE I SAID, 1701 01:28:38,440 --> 01:28:40,400 VIP IS ONE OF THE MANY FACTORS 1702 01:28:40,400 --> 01:28:44,280 MAYBE AND IT DOESN'T EXPLAIN THE 1703 01:28:44,280 --> 01:28:47,320 ENTIRE RESPONSE SO WHAT OTHER 1704 01:28:47,320 --> 01:28:49,560 MOLECULES ARE INVOLVED? 1705 01:28:49,560 --> 01:28:51,120 AND THEN THE MAIN QUESTION 1706 01:28:51,120 --> 01:29:01,440 ACTUALLY HAS NOT BEEN SOLVED SO 1707 01:29:01,440 --> 01:29:03,440 OS MOLE TESTING WE DO KNOW WHAT 1708 01:29:03,440 --> 01:29:05,800 CELLS ARE SENSING IT AND HOW VIP 1709 01:29:05,800 --> 01:29:06,920 DETECTION IN THE VEIN WE KNOW 1710 01:29:06,920 --> 01:29:09,000 THAT THE RECEPTORS BUT HOW DOES 1711 01:29:09,000 --> 01:29:13,640 THE RECEPTORS ACTIVATE THIS 1712 01:29:13,640 --> 01:29:15,040 VAGAL KNEW ON BECAUSE THEY DON'T 1713 01:29:15,040 --> 01:29:17,160 EXPRESS THE VIP RECEPTORS SO HOW 1714 01:29:17,160 --> 01:29:18,560 DO THEY COMMUNICATE EACH OTHER 1715 01:29:18,560 --> 01:29:26,720 SO THERE ARE MANY QUESTIONS WE 1716 01:29:26,720 --> 01:29:28,000 ARE TRYING TO CHALLENGE THOSE 1717 01:29:28,000 --> 01:29:30,720 AND I'D LIKE TO THANK MY LAB 1718 01:29:30,720 --> 01:29:36,880 MEMBERS AND ESPECIALLY THE WORK 1719 01:29:36,880 --> 01:29:42,800 AND HE IS AN EXCELLENT SURGEON 1720 01:29:42,800 --> 01:29:44,200 AND SHE GOT COMMISSIONED IN 1721 01:29:44,200 --> 01:29:48,680 JAPAN AND OTHER MEMBERS AND 1722 01:29:48,680 --> 01:29:51,040 THANK YOU. 1723 01:29:51,040 --> 01:29:52,880 [APPLAUSE] 1724 01:29:52,880 --> 01:29:56,480 THANK YOU AND NICE PRESENTATION. 1725 01:29:56,480 --> 01:29:58,600 AS Dr. JO IS COMING UP WE HAVE 1726 01:29:58,600 --> 01:29:59,920 ROOM FOR ONE MORE QUESTION. 1727 01:29:59,920 --> 01:30:03,760 ANYONE HAVE A QUESTION HERE IN 1728 01:30:03,760 --> 01:30:06,680 THE ROOM? 1729 01:30:06,680 --> 01:30:08,840 >>IS THERE A POSSIBILITY YOU 1730 01:30:08,840 --> 01:30:10,000 CONSIDER GIVEN THE RESULTS THAT 1731 01:30:10,000 --> 01:30:14,000 WE HAVE ACTUALLY A MECHANISM FOR 1732 01:30:14,000 --> 01:30:16,960 SENSING WATER LIKE IMAGINE THIS 1733 01:30:16,960 --> 01:30:26,920 SAME IS FOR SENSING SUCROSE THAT 1734 01:30:26,920 --> 01:30:30,600 IT'S NOT EVEN, IT'S IMPORTANT 1735 01:30:30,600 --> 01:30:32,520 THAT YOU WOULD BE SOME KIND OF 1736 01:30:32,520 --> 01:30:33,800 SIGNALING MECHANISM THAT IT 1737 01:30:33,800 --> 01:30:38,400 DOESN'T NEED TO DETECT 1738 01:30:38,400 --> 01:30:38,680 OSMOLARIS? 1739 01:30:38,680 --> 01:30:39,920 >>IT'S TRUE. 1740 01:30:39,920 --> 01:30:45,800 I SAID OSMOLALITY AS A GENERAL 1741 01:30:45,800 --> 01:30:48,000 STIMULUS THAT WATER IF IT'S SELF 1742 01:30:48,000 --> 01:30:50,520 IS SENSED BY SOME CHANNEL. 1743 01:30:50,520 --> 01:30:52,160 AND SO THAT'S FASCINATING 1744 01:30:52,160 --> 01:30:53,240 POSSIBILITY AND WE'RE LOOKING 1745 01:30:53,240 --> 01:30:53,960 INTO THAT. 1746 01:30:53,960 --> 01:30:57,400 YEAH, DEFINITELY. 1747 01:30:57,400 --> 01:31:03,280 THANK YOU. 1748 01:31:03,280 --> 01:31:05,720 >>NEXT SPEAKER, PLEASE. 1749 01:31:05,720 --> 01:31:09,160 MY PRESENTATION IS FUNCTIONAL 1750 01:31:09,160 --> 01:31:11,520 IDENTIFICATION OF VAGAL SENSORY 1751 01:31:11,520 --> 01:31:15,520 NEURONS INNERVATING THE LIVER. 1752 01:31:15,520 --> 01:31:17,880 SO, THE VITAL ORGANS THEY 1753 01:31:17,880 --> 01:31:19,880 CONTROL DIVERSE FUNCTIONS AND 1754 01:31:19,880 --> 01:31:26,640 SUCH AS ENERGY AND HOMEOSTASIS 1755 01:31:26,640 --> 01:31:30,440 AND THE BRAIN FUNCTION AS WELL. 1756 01:31:30,440 --> 01:31:33,680 SO TO CATCH ON THE IDEAS OF 1757 01:31:33,680 --> 01:31:37,080 FUTURE REGULATED BY THE BRAIN. 1758 01:31:37,080 --> 01:31:40,480 IF SO, THE INTEROCEPTION 1759 01:31:40,480 --> 01:31:43,560 SIGNALING BETWEEN THE VIVA AND 1760 01:31:43,560 --> 01:31:46,760 VAGAL SENSORY NEURONS. 1761 01:31:46,760 --> 01:31:48,960 SO OUR AIM IS ANY ONE TO 1762 01:31:48,960 --> 01:31:50,880 DETERMINE THE MOLECULAR AND 1763 01:31:50,880 --> 01:31:52,680 CELLULAR IDENTITY OF LIVER 1764 01:31:52,680 --> 01:31:56,320 PROJECT IN SENSORY NEURONS AND 1765 01:31:56,320 --> 01:32:00,080 IS THE FUNCTION CONSISTS OF LOSS 1766 01:32:00,080 --> 01:32:01,840 OF FUNCTION OF RIVER-BRAIN 1767 01:32:01,840 --> 01:32:04,080 NEURAL CIRCUIT. 1768 01:32:04,080 --> 01:32:09,080 WE USE THE TWO MODEL ONE IS A 1769 01:32:09,080 --> 01:32:13,720 LABEL TO ANIMAL AND SENSE ROW ON 1770 01:32:13,720 --> 01:32:17,920 SPECIFIC BIND IN PROTEINS SO 1771 01:32:17,920 --> 01:32:25,600 MOST IS THE OTHER IS CALCA AND 1772 01:32:25,600 --> 01:32:31,880 THE WE USE RETROGRADE AAV AND 1773 01:32:31,880 --> 01:32:37,320 SUCH AS LIVER PROTECTING AND THE 1774 01:32:37,320 --> 01:32:41,560 TO REGULATE THEIR ACTIVITIES AND 1775 01:32:41,560 --> 01:32:44,320 PROTEIN TO RECORD THE ACTIVITY 1776 01:32:44,320 --> 01:32:49,640 OF THE LIVER PROTECT NEURON AND 1777 01:32:49,640 --> 01:32:53,360 IT TO A TO CELL ACTIVELY AND 1778 01:32:53,360 --> 01:32:58,080 PROJECTING SENSORY NEURONS. 1779 01:32:58,080 --> 01:33:01,120 SO I'LL SHOW YOU THE VIVO 1780 01:33:01,120 --> 01:33:05,040 PROJECT IN NEURONS AND IT'S USED 1781 01:33:05,040 --> 01:33:07,960 WITH THE CALCA AND SENSORY 1782 01:33:07,960 --> 01:33:12,760 ANIMAL AND WE INJECTED THE 1783 01:33:12,760 --> 01:33:15,480 RETROGRADE AA HAVE AND THE 1784 01:33:15,480 --> 01:33:19,360 PROTEINS AND SO YOU CAN PROBE 1785 01:33:19,360 --> 01:33:20,760 THE LIVER PROJECT AND YOU SEE 1786 01:33:20,760 --> 01:33:24,400 HERE WE FOUND VERY SMALL NEURON 1787 01:33:24,400 --> 01:33:28,520 AND PROJECTED TO THE LIVER. 1788 01:33:28,520 --> 01:33:34,000 WE FOUND IT VERY STRONG AND 1789 01:33:34,000 --> 01:33:37,040 SIGNAL INTO THE SITE AND YOU SEE 1790 01:33:37,040 --> 01:33:43,240 HERE THE POSITIVE KNOB PRESENT 1791 01:33:43,240 --> 01:33:47,640 OF THE NEURONS. 1792 01:33:47,640 --> 01:33:50,400 SO SOME OF THE INNOVATION AND 1793 01:33:50,400 --> 01:33:54,000 MORE IMPORTANT REALLY SO THEY 1794 01:33:54,000 --> 01:33:57,880 LOCATED AROUND THE PROTEIN AND 1795 01:33:57,880 --> 01:34:04,720 THEY SEE SNAP INNOVATIONS. 1796 01:34:04,720 --> 01:34:07,800 WE FOUND THE. 1797 01:34:07,800 --> 01:34:08,920 >>Commissioner Rubio: AND THIY 1798 01:34:08,920 --> 01:34:13,040 IMPORTANT AND THEY CONTAIN 1799 01:34:13,040 --> 01:34:15,200 NUTRIENTS AND THE WATER IS 1800 01:34:15,200 --> 01:34:18,560 SENSORY INNOVATION AND CAN SENSE 1801 01:34:18,560 --> 01:34:22,960 AND DETECT TO THE SIGNAL AND SO 1802 01:34:22,960 --> 01:34:29,320 WE FOUND THAT THIS IS IT'S' 1803 01:34:29,320 --> 01:34:36,120 UNIQUE AND SO IT'S NETWORK SO 1804 01:34:36,120 --> 01:34:39,200 THIS IS THE SYNAPSIS AND THIS IS 1805 01:34:39,200 --> 01:34:42,560 FORCED THE DEM ON STRAW STATION 1806 01:34:42,560 --> 01:34:44,600 AND AND WE WANT TO MAKE SURE 1807 01:34:44,600 --> 01:34:52,840 THAT THIS IS A TRUE AND SYNAPSIS 1808 01:34:52,840 --> 01:34:56,280 AND WE CHANGED THE TRANSPORT AND 1809 01:34:56,280 --> 01:35:00,480 YOU SEE HERE AND THIS IS THE 1810 01:35:00,480 --> 01:35:03,680 SAME SO THEY MAKE THE SNAP TEAM 1811 01:35:03,680 --> 01:35:09,160 NETWORK AND THE NEURONS BUT ALSO 1812 01:35:09,160 --> 01:35:16,040 WE FOUND THAT MAKE PERCENT SAME 1813 01:35:16,040 --> 01:35:18,880 SNAP SIS SO THIS IS INDICATE 1814 01:35:18,880 --> 01:35:28,920 THAT IN CONTRAST TO THE SEPTIC 1815 01:35:28,920 --> 01:35:31,920 SENSATION AFTER INPUT AND OUR 1816 01:35:31,920 --> 01:35:35,560 DATA SUGGESTS THAT THE 1817 01:35:35,560 --> 01:35:39,000 SIGNIFICANT UPDATE INPUT SO NEXT 1818 01:35:39,000 --> 01:35:41,040 THERE IS A COMMUNICATION BETWEEN 1819 01:35:41,040 --> 01:35:45,080 THE LIVER AND THE VAGAL SENSORY 1820 01:35:45,080 --> 01:35:48,280 NEURONS SO STUDY THIS PROBLEM 1821 01:35:48,280 --> 01:35:51,600 THIS POSSIBILITY AND WE 1822 01:35:51,600 --> 01:35:53,920 SELECTIVELY PRESSED SENSING AND 1823 01:35:53,920 --> 01:36:00,600 ON IN NEURON AND THE LIVER AND 1824 01:36:00,600 --> 01:36:03,320 WE ALSO DEVELOPED AAV VIRUS SO 1825 01:36:03,320 --> 01:36:08,520 WE EXPRESSED THE TODAY THE 1826 01:36:08,520 --> 01:36:11,720 RECEPTOR ONLY IN BY USING THE 1827 01:36:11,720 --> 01:36:15,120 PROMOTER WHICH IS THE 1828 01:36:15,120 --> 01:36:16,560 SPECIFICITY SO WE CAN EXPRESS 1829 01:36:16,560 --> 01:36:23,840 THE GS COUPLED RECEPTORS AND WE 1830 01:36:23,840 --> 01:36:28,000 EXPRESS SENSING PROTEIN IN 1831 01:36:28,000 --> 01:36:30,600 NEURONS AND DOING MAJOR 1832 01:36:30,600 --> 01:36:34,600 SIGNALING FROM THE GANGLIA AND 1833 01:36:34,600 --> 01:36:38,320 WE SEE HERE, THIS IS THE WAY THE 1834 01:36:38,320 --> 01:36:48,720 IP INJECTION AND THIS IS 1835 01:36:49,120 --> 01:36:50,680 ACTIVATION OF RECEPTORS 1836 01:36:50,680 --> 01:36:54,920 INCREASES SIGNALING THE LIVER 1837 01:36:54,920 --> 01:37:00,560 REDICTIONARYING AND SO FROM IS 1838 01:37:00,560 --> 01:37:11,000 SOCIETY AND AND I SENSES. 1839 01:37:14,640 --> 01:37:19,640 BUT SO WE USE THE SAME PROTOCOL 1840 01:37:19,640 --> 01:37:22,720 WE FOUND LARGE ENOUGH INNOVATION 1841 01:37:22,720 --> 01:37:28,840 IN THE AREA AND SO YOU FOUND THE 1842 01:37:28,840 --> 01:37:30,680 AREA THAT CAN THE SAMPLE AS YOU 1843 01:37:30,680 --> 01:37:36,320 SEE HERE, SOME OF THE NEURON 1844 01:37:36,320 --> 01:37:39,320 RECEIVER AND FROM THE PROJECTING 1845 01:37:39,320 --> 01:37:45,000 THAT ASSOCIATED NEURONS SO THIS 1846 01:37:45,000 --> 01:37:52,680 INDICATES THIS SHOULD ALSO SEND 1847 01:37:52,680 --> 01:38:03,200 BACK THE LIVER AND OTHER ORGANS. 1848 01:38:03,200 --> 01:38:06,160 WE CAN FUNCTION THE SENSORY 1849 01:38:06,160 --> 01:38:07,920 NEURON SO TO STUDY THIS 1850 01:38:07,920 --> 01:38:12,280 POSSIBILITY WE USED THIS TIME 1851 01:38:12,280 --> 01:38:15,640 LIVER ANIMAL AND TEST PAGE 3 SO 1852 01:38:15,640 --> 01:38:19,520 WE EXPRESSED THE ONLY IN VIVO 1853 01:38:19,520 --> 01:38:24,920 PROTECTING SENSITIVE NEURONS AND 1854 01:38:24,920 --> 01:38:27,240 THEN WE KEPT DIET TO SEE THE 1855 01:38:27,240 --> 01:38:30,320 SENSE ROW NEURON AND TO ACCESS 1856 01:38:30,320 --> 01:38:37,680 OUR KNEE TREE ENTERS AND YOU SEE 1857 01:38:37,680 --> 01:38:41,880 HERE, SO THEY BECOME OVER 1858 01:38:41,880 --> 01:38:43,840 HOWEVER WE FOUND THAT MICE 1859 01:38:43,840 --> 01:38:47,680 WITHOUT THE PREDICTING AND 1860 01:38:47,680 --> 01:38:54,000 ACCESSORY NEURONS THEY AND AND 1861 01:38:54,000 --> 01:39:00,840 THIS IS TO THE INCREASING 1862 01:39:00,840 --> 01:39:06,000 BECAUSE THERE IS NO DIFFERENCE 1863 01:39:06,000 --> 01:39:08,160 IN THE MESS BETWEEN THE GROWTH. 1864 01:39:08,160 --> 01:39:09,680 WE FOUND THE SAME RESULT IN 1865 01:39:09,680 --> 01:39:17,080 FEMALE ANIMALS. 1866 01:39:17,080 --> 01:39:19,440 WE GET THAT EFFORT IN THE LIVER 1867 01:39:19,440 --> 01:39:24,000 SO THIS IS A CONTROL ANIMAL WE 1868 01:39:24,000 --> 01:39:28,280 DID THE SAY LIPID AND WE SEE 1869 01:39:28,280 --> 01:39:33,640 HERE, MANY EMPTY SPACES IN THE 1870 01:39:33,640 --> 01:39:38,000 PLASMA OF THE AND THE 1871 01:39:38,000 --> 01:39:39,640 ACCUMULATION IN THE WE FOUND 1872 01:39:39,640 --> 01:39:43,400 LARGE ACCUMULATION AROUND THE 1873 01:39:43,400 --> 01:39:47,840 CENTER EVENT AND THIS IS THE 1874 01:39:47,840 --> 01:39:55,720 LIVER AND WE FOUND ACCUMULATION 1875 01:39:55,720 --> 01:39:59,640 IN THE LIVER AND ALSO WE MAJOR 1876 01:39:59,640 --> 01:40:03,120 THE LIVER WE FOUND A SIGNIFICANT 1877 01:40:03,120 --> 01:40:08,040 DECREASE AND IN THE LIVER SO 1878 01:40:08,040 --> 01:40:14,080 THIS INDICATES THE LIVER. 1879 01:40:14,080 --> 01:40:16,120 AND THEN WHEN I START WITH THIS 1880 01:40:16,120 --> 01:40:22,000 STUDY I PROMISE AND I'M GOING TO 1881 01:40:22,000 --> 01:40:26,480 HOW THIS SIGNAL ON THE REGULATOR 1882 01:40:26,480 --> 01:40:29,320 THE FRAME FUNCTION AND WE HAVE A 1883 01:40:29,320 --> 01:40:32,120 TESTER SO CHANGE FROM TESTING TO 1884 01:40:32,120 --> 01:40:36,320 ACCESS INGEST LIKE BEHAVIOR OR 1885 01:40:36,320 --> 01:40:39,160 WILLINGNESS. 1886 01:40:39,160 --> 01:40:40,840 SO IT'S THIS IS A CONTROL ANIMAL 1887 01:40:40,840 --> 01:40:42,880 AS YOU SEE HERE, CONTROL ANIMAL 1888 01:40:42,880 --> 01:40:48,120 STAY IN THE AREA CLOSE TO WHERE 1889 01:40:48,120 --> 01:40:50,560 HOWEVER MOUSE WITHOUT PRO 1890 01:40:50,560 --> 01:40:52,640 DICTION NEURONS AND THEY WILL 1891 01:40:52,640 --> 01:40:55,040 LINK TO EXPLORE IN THE CENTRAL 1892 01:40:55,040 --> 01:40:58,560 AREA SO WE FOUND THAT THERE'S AN 1893 01:40:58,560 --> 01:41:02,440 INCREASE OF ACTIVITY AND THE 1894 01:41:02,440 --> 01:41:05,640 MOUSE STAYED LONGER IN CENTER 1895 01:41:05,640 --> 01:41:07,920 AREA. 1896 01:41:07,920 --> 01:41:10,760 SO THIS IS PROJECT IN SENSE ROW 1897 01:41:10,760 --> 01:41:14,000 NEURONS INCREASE IN ACTIVITY AND 1898 01:41:14,000 --> 01:41:21,360 WHILE REDUCING ANXIETY LIKE 1899 01:41:21,360 --> 01:41:22,080 BEHAVIOR. 1900 01:41:22,080 --> 01:41:23,040 WE FOUND IT SIGNIFICANT INPUT 1901 01:41:23,040 --> 01:41:25,920 FROM THE SENSORY NEURONS AND 1902 01:41:25,920 --> 01:41:29,800 ACTIVATION AND THE RECEPTORS AND 1903 01:41:29,800 --> 01:41:32,120 ON THE AND THIS SUBSEQUENT TO 1904 01:41:32,120 --> 01:41:36,760 THE ACTIVATED THE SENSE ROW 1905 01:41:36,760 --> 01:41:47,280 NEURON THIS SIGNALING AND THIS 1906 01:42:12,520 --> 01:42:14,720 WORK CANNOT BE DONE WITH HALF 1907 01:42:14,720 --> 01:42:18,400 THE DOCTOR SCHWARTZ AND MY 1908 01:42:18,400 --> 01:42:18,680 POSTDOCS. 1909 01:42:18,680 --> 01:42:20,600 THANK YOU SO MUCH FOR YOUR 1910 01:42:20,600 --> 01:42:20,880 ATTENTION. 1911 01:42:20,880 --> 01:42:25,040 [APPLAUSE] 1912 01:42:25,040 --> 01:42:27,000 >>THANK YOU TO ALL SPEAKERS. 1913 01:42:27,000 --> 01:42:33,840 WE HAVE ONE QUESTION. 1914 01:42:33,840 --> 01:42:38,360 >>VERY INTERESTING DATA AND 1915 01:42:38,360 --> 01:42:40,000 EVEN -- OF VAGAL INNOVATION TO 1916 01:42:40,000 --> 01:42:42,120 THE LIVER. 1917 01:42:42,120 --> 01:42:45,720 SO, YOU SHOWED THAT THE LIVER 1918 01:42:45,720 --> 01:42:49,280 PROJECTION CAN ALLEVIATE THE 1919 01:42:49,280 --> 01:42:51,040 PHENOTYPE BUT YOU SHOW THAT 1920 01:42:51,040 --> 01:42:52,840 LOCAL MOTION FOR INCREASE SO CAN 1921 01:42:52,840 --> 01:42:57,880 YOU EXPLAIN THAT INCREASED 1922 01:42:57,880 --> 01:42:58,800 LOCOMOTION? 1923 01:42:58,800 --> 01:43:00,200 >>THAT'S THE DIFFERENCE. 1924 01:43:00,200 --> 01:43:03,600 THIS IS ACTIVITY AND WE DID OPEN 1925 01:43:03,600 --> 01:43:05,160 TO THE TEST. 1926 01:43:05,160 --> 01:43:07,200 THEY HAVE INCREASED THE ACTIVITY 1927 01:43:07,200 --> 01:43:12,240 BUT WHEN YOU LOOK AT WHO LOCO 1928 01:43:12,240 --> 01:43:15,440 ACTIVITY THERE'S A SIGNIFICANT 1929 01:43:15,440 --> 01:43:22,120 INCREASE IN DECREASE IN THE 1930 01:43:22,120 --> 01:43:22,360 ACTIVITY. 1931 01:43:22,360 --> 01:43:24,280 >>WE'RE GOING TO HAVE NOW AN 1932 01:43:24,280 --> 01:43:26,960 OVER ALL QUESTION FOR 10 MINUTES 1933 01:43:26,960 --> 01:43:29,000 BECAUSE WE'RE GOING TO SHORTEN 1934 01:43:29,000 --> 01:43:32,200 IT A LITTLE BIT SO MAYBE YOU CAN 1935 01:43:32,200 --> 01:43:33,000 START YOUR QUESTIONS. 1936 01:43:33,000 --> 01:43:33,840 >>THAT'S GREAT. 1937 01:43:33,840 --> 01:43:36,600 >>LET ME INTRODUCE I HAVE A 1938 01:43:36,600 --> 01:43:36,880 QUESTION. 1939 01:43:36,880 --> 01:43:42,240 SO WHEN YOU APPLY THE LIVER 1940 01:43:42,240 --> 01:43:46,840 PROJECTION SENSORY VAGUS 1941 01:43:46,840 --> 01:43:47,080 NEURONS. 1942 01:43:47,080 --> 01:43:48,720 WHAT HAPPENS WITH THE ANIMALS? 1943 01:43:48,720 --> 01:43:51,720 DOES ANIMAL EAT LESSOR BE MORE 1944 01:43:51,720 --> 01:43:52,320 ACTIVE? 1945 01:43:52,320 --> 01:43:57,160 >>THAT'S A GOOD QUESTION. 1946 01:43:57,160 --> 01:44:00,960 WE LOOK AT SENSORY NEURONS AND 1947 01:44:00,960 --> 01:44:04,400 ALSO WE DID SUPPRESS THE 1948 01:44:04,400 --> 01:44:06,800 RECEPTORS COUPLED WITH THE 1949 01:44:06,800 --> 01:44:11,320 RECEPTOR IN CGIP. 1950 01:44:11,320 --> 01:44:13,000 WHEN YOU ARE ACTIVATING THE 1951 01:44:13,000 --> 01:44:16,440 SHORT TERM WITH RECEPTORS, THEY 1952 01:44:16,440 --> 01:44:17,120 EAT MORE. 1953 01:44:17,120 --> 01:44:21,040 THEY EAT MORE, YEAH. 1954 01:44:21,040 --> 01:44:24,120 IN THIS HYPER FEEDING BECAUSE 1955 01:44:24,120 --> 01:44:27,840 THERE'S BIG DIFFERENCE SO YOU 1956 01:44:27,840 --> 01:44:30,720 CANNOT MEASURE HOW MUCH THEY EAT 1957 01:44:30,720 --> 01:44:32,760 BECAUSE THE DIFFERENCE IS VERY 1958 01:44:32,760 --> 01:44:36,920 BIG IN TERMS OF EVALUATED SO WE 1959 01:44:36,920 --> 01:44:40,600 SHOULD CALCULATE NORMALIZE IT 1960 01:44:40,600 --> 01:44:44,440 AND THEN WHEN YOU GET -- WHEN 1961 01:44:44,440 --> 01:44:48,880 YOU NORMALIZE THE FOOD INTAKE, 1962 01:44:48,880 --> 01:44:55,520 THEY EAT THE SAME. 1963 01:44:55,520 --> 01:44:55,880 THIS CALORIES. 1964 01:44:55,880 --> 01:44:58,240 >>SO YOU ARE CHANGING THE 1965 01:44:58,240 --> 01:44:58,760 METABOLISM? 1966 01:44:58,760 --> 01:44:59,680 >>SORRY? 1967 01:44:59,680 --> 01:45:03,160 >>THE INTERVENTION, YOU DID 1968 01:45:03,160 --> 01:45:05,200 CHANGE THE METABOLISM? 1969 01:45:05,200 --> 01:45:07,600 >>YEAH. 1970 01:45:07,600 --> 01:45:11,040 ACTUALLY, WE ARE DOING THAT THE 1971 01:45:11,040 --> 01:45:15,320 CALORIE EXTREME WAS SO WE FOUND 1972 01:45:15,320 --> 01:45:17,600 VERY BIG DIFFERENCE OF ACTIVITY 1973 01:45:17,600 --> 01:45:21,080 AND ENERGY EXPENDITURE. 1974 01:45:21,080 --> 01:45:23,800 >>WE ARE GOING TO READ SOME 1975 01:45:23,800 --> 01:45:25,640 QUESTIONS FROM THE CHAT RIGHT 1976 01:45:25,640 --> 01:45:25,800 NOW. 1977 01:45:25,800 --> 01:45:28,200 SO IF YOU WANT YOU CAN SIT DOWN 1978 01:45:28,200 --> 01:45:30,680 BUT YOU CAN ALSO STAY THERE 1979 01:45:30,680 --> 01:45:31,720 BECAUSE IT'S GOING TO BE FOR 1980 01:45:31,720 --> 01:45:32,120 EVERYONE. 1981 01:45:32,120 --> 01:45:35,640 THE FIRST QUESTION IS TO Dr. 1982 01:45:35,640 --> 01:45:40,960 LIU AND Dr. CHEN. 1983 01:45:40,960 --> 01:45:46,080 HAVE YOU CONSIDERED UNILATERAL 1984 01:45:46,080 --> 01:45:47,840 VAGOTOMY WHETHER SENDING INPUTS 1985 01:45:47,840 --> 01:45:52,400 PROJECT TO BOTH SIDES OF THE 1986 01:45:52,400 --> 01:45:52,600 BRAIN? 1987 01:45:52,600 --> 01:45:57,320 >>WE DID BILATERAL. 1988 01:45:57,320 --> 01:45:59,720 WE HAVE NOT TRIED UNILATERAL BUT 1989 01:45:59,720 --> 01:46:01,040 THAT'S A GOOD SUGGESTION AND 1990 01:46:01,040 --> 01:46:04,960 WE'LL EXPLORE THAT. 1991 01:46:04,960 --> 01:46:10,920 >>NEXT QUESTION IS FOR Dr. 1992 01:46:10,920 --> 01:46:11,760 ARAUJO. 1993 01:46:11,760 --> 01:46:13,560 THE WORK OF Dr. LIU SUGGESTS 1994 01:46:13,560 --> 01:46:15,440 THAT STOMACH TO BRAIN 1995 01:46:15,440 --> 01:46:16,520 INTEROCEPTION IS ALMOST 1996 01:46:16,520 --> 01:46:19,400 COMPLETELY ABOLISHED SUGGESTING 1997 01:46:19,400 --> 01:46:22,960 A CRITICAL ROLE OF THE ARM OF 1998 01:46:22,960 --> 01:46:27,600 THE VAGUS NERVE IN SIGNALING 1999 01:46:27,600 --> 01:46:30,480 THESE FINDING APPEARS TO BE AT 2000 01:46:30,480 --> 01:46:37,720 ODDS WITH THE DATA BY Dr. 2001 01:46:37,720 --> 01:46:40,280 ARAUJ SO SAYING IT DOES NOT 2002 01:46:40,280 --> 01:46:41,720 CONTROL FULLNESS TO THE BRAIN. 2003 01:46:41,720 --> 01:46:42,600 PLEASE DISCUSS WHAT KIND OF 2004 01:46:42,600 --> 01:46:46,360 LEVEL OF SENSORY WERE ABLATED IN 2005 01:46:46,360 --> 01:46:48,080 THE DTX APPROACH. 2006 01:46:48,080 --> 01:46:51,080 THOSE GO TO BOTH BASICALLY. 2007 01:46:51,080 --> 01:46:54,440 Dr. OKA AND Dr. LIU. 2008 01:46:54,440 --> 01:46:58,040 >>SO, IF WE UNDERSTOOD THE 2009 01:46:58,040 --> 01:46:59,920 FINDINGS CORRECTLY WHAT WAS 2010 01:46:59,920 --> 01:47:02,560 ABOLISHED IS THE SYNCHRONY IN 2011 01:47:02,560 --> 01:47:06,080 SIGNAL BETWEEN STOMACH MOVEMENT 2012 01:47:06,080 --> 01:47:08,920 AND THE BRAIN OSCILLATION, 2013 01:47:08,920 --> 01:47:09,240 RIGHT. 2014 01:47:09,240 --> 01:47:11,520 SO THIS IS A VERY INTERESTING 2015 01:47:11,520 --> 01:47:11,920 QUESTION. 2016 01:47:11,920 --> 01:47:14,560 WE DON'T KNOW EXACTLY WHAT THIS 2017 01:47:14,560 --> 01:47:17,360 SYNCHRONY MEANS IN TERMS FOR THE 2018 01:47:17,360 --> 01:47:18,760 BRAIN AND WHAT FUNCTIONS IT MAY 2019 01:47:18,760 --> 01:47:24,360 BE PERFORMING SO I THINK THAT IT 2020 01:47:24,360 --> 01:47:27,800 DOES NOT MEAN OSCILLATIONS AND 2021 01:47:27,800 --> 01:47:35,320 TOOKING FOR THEY MAY BE MOR 2022 01:47:35,320 --> 01:47:39,000 COMPLEX BECAUSE OF GUT MOVEMENT 2023 01:47:39,000 --> 01:47:40,800 AND THE FACT OF THAT YOU WILL 2024 01:47:40,800 --> 01:47:44,800 HAVE THIS CONSCIOUS PERCEPTION 2025 01:47:44,800 --> 01:47:48,680 OF DISTINCTION MEDIATED BY 2026 01:47:48,680 --> 01:47:52,160 DORRAL ROUTE GANGLIA IS MORE 2027 01:47:52,160 --> 01:47:53,800 CONSISTENT WITH WHAT WE KNOW 2028 01:47:53,800 --> 01:47:55,000 ABOUT THE BLADDER, WHICH 2029 01:47:55,000 --> 01:47:56,840 PRODUCES VERY SIMILAR SENSATIONS 2030 01:47:56,840 --> 01:47:59,880 AND VERY SIMILAR TYPES OF 2031 01:47:59,880 --> 01:48:01,840 BEHAVIOR WITH IN THIS CASE WE 2032 01:48:01,840 --> 01:48:04,440 KNOW IT'S ENTIRELY DEPENDENT ON 2033 01:48:04,440 --> 01:48:08,520 THE DORRAL ROUTE GANGLIA SO I 2034 01:48:08,520 --> 01:48:10,640 THINK IT'S A QUESTION TO BE 2035 01:48:10,640 --> 01:48:14,840 INVESTIGATED IN THE FUTURE FOR 2036 01:48:14,840 --> 01:48:22,080 THE DORRAL ROUTE GANGLIA 2037 01:48:22,080 --> 01:48:24,560 LESIONS, IN WITHIN WAY WE 2038 01:48:24,560 --> 01:48:28,920 INJECTED DIRECTLY INTO THE 2039 01:48:28,920 --> 01:48:31,280 THORACIC DOR SO ROUTE GANGLIA 2040 01:48:31,280 --> 01:48:33,520 WHERE MOST OF THE INTEROCEPTION 2041 01:48:33,520 --> 01:48:35,560 TARGETING THE STOMACH IS LOCATED 2042 01:48:35,560 --> 01:48:39,640 AND WE ALSO PERFORMED INJECTIONS 2043 01:48:39,640 --> 01:48:41,480 OF THE TOXIN AND THEY SEEM TO 2044 01:48:41,480 --> 01:48:44,920 PRODUCE VERY SIMILAR EFFECTS. 2045 01:48:44,920 --> 01:48:48,000 SO, WE USED A BALLOON THAT CAUSE 2046 01:48:48,000 --> 01:48:53,200 A CERTAIN PRESSURE ABOUT 2047 01:48:53,200 --> 01:48:55,240 10 MILLIGRAMS MERCURY THAT WE 2048 01:48:55,240 --> 01:49:01,560 KNOW IS THE THRESHOLD IN ANIMALS 2049 01:49:01,560 --> 01:49:03,560 WILL STOP EAT NORTH A FREELY 2050 01:49:03,560 --> 01:49:06,120 BEHAVING SETING AND THE VAGAL 2051 01:49:06,120 --> 01:49:08,800 LESIONS DID NOT DISRUPT THE 2052 01:49:08,800 --> 01:49:10,800 ABILITY OF THE ANIMALS TO 2053 01:49:10,800 --> 01:49:14,720 INFLATE THE BALLOON UP TO 2054 01:49:14,720 --> 01:49:15,640 10 MILLIGRAMS MERCURY. 2055 01:49:15,640 --> 01:49:18,200 SO IT'S AN OPEN QUESTION TO 2056 01:49:18,200 --> 01:49:20,640 INTERPRET THE FUNCTIONALITY OF 2057 01:49:20,640 --> 01:49:22,400 THE CORRELATION BETWEEN GUT AND 2058 01:49:22,400 --> 01:49:24,080 BRAIN, WHICH IS VERY 2059 01:49:24,080 --> 01:49:24,400 INTERESTING. 2060 01:49:24,400 --> 01:49:27,960 IT MAY NOT BE SIMPLY JUST 2061 01:49:27,960 --> 01:49:29,680 DETECTING DISTINCTION ON ORGAN 2062 01:49:29,680 --> 01:49:35,520 VALUE PER SE. 2063 01:49:35,520 --> 01:49:38,080 >>I DEGREE THESE ARE TWO 2064 01:49:38,080 --> 01:49:39,600 DIFFERENT SET OF PHENOMENON AND 2065 01:49:39,600 --> 01:49:42,200 ONE IS THE MOW TILL TEE AND THE 2066 01:49:42,200 --> 01:49:51,000 OTHER REGARDING THE GAS TICK GAS 2067 01:49:51,000 --> 01:49:51,240 TENSION. 2068 01:49:51,240 --> 01:49:53,880 AND WE THINK THAT THE INTRINSIC 2069 01:49:53,880 --> 01:49:57,080 AND SPONTANEOUS IN REAL-TIME 2070 01:49:57,080 --> 01:49:59,320 BRAIN-GUT SYNCHRONY, IS AN 2071 01:49:59,320 --> 01:50:00,480 INTRIGUING PHENOMENON. 2072 01:50:00,480 --> 01:50:04,120 IT'S LIKELY VERY USEFUL MARKER 2073 01:50:04,120 --> 01:50:08,560 OF THE GUT-BRAIN INTERACTION. 2074 01:50:08,560 --> 01:50:10,720 IT REFLECTS MUCH MORE REGARDING 2075 01:50:10,720 --> 01:50:13,840 MOW TILL TEE AND THE A ARYTHMIC 2076 01:50:13,840 --> 01:50:16,280 CHANGES OF GASTRIC MOVEMENTS AND 2077 01:50:16,280 --> 01:50:18,640 HOW IT'S SENSED BY AND LIKELY 2078 01:50:18,640 --> 01:50:21,440 POTENTIALLY REGULATED BY THE 2079 01:50:21,440 --> 01:50:22,040 BRAIN. 2080 01:50:22,040 --> 01:50:26,280 AND THAT IS DIFFERENT FROM THE 2081 01:50:26,280 --> 01:50:28,520 FINDINGS YOU JUST REPORTED 2082 01:50:28,520 --> 01:50:30,560 REGARDING THE DORRAL ROAD 2083 01:50:30,560 --> 01:50:32,720 GANGLIA FOR GASTRIC DIS TENSION. 2084 01:50:32,720 --> 01:50:34,200 THAT'S MY COMMENT AND I KNOW MY 2085 01:50:34,200 --> 01:50:36,520 COLLEAGUES WOULD HAVE OTHER 2086 01:50:36,520 --> 01:50:37,600 INPUT AS WELL. 2087 01:50:37,600 --> 01:50:39,680 >>JUST ONE QUICK NOTE, IN FACT 2088 01:50:39,680 --> 01:50:41,200 THEY MAY NEED THE OPPOSITE 2089 01:50:41,200 --> 01:50:44,560 BECAUSE DURING DISTINCTION THE 2090 01:50:44,560 --> 01:50:46,040 MOW DILL TEE IS DISRUPT SO 2091 01:50:46,040 --> 01:50:48,160 PROBABLY DURING THE DISTINCTION 2092 01:50:48,160 --> 01:50:50,680 THIS MAY BE DISRUPTED IN TERMS 2093 01:50:50,680 --> 01:50:53,000 OF SYNCHRONY BETWEEN THE TWO? 2094 01:50:53,000 --> 01:50:56,720 >>WHEN WE ARE DOING THIS 2095 01:50:56,720 --> 01:50:57,240 INTEROCEPTION GRANT WE DID 2096 01:50:57,240 --> 01:50:59,920 SEVERAL STUDIES WITH GASTRO 2097 01:50:59,920 --> 01:51:00,840 DETENTION IS TRICKERY. 2098 01:51:00,840 --> 01:51:03,840 WHEN YOU HAVE THE STOMACH AT THE 2099 01:51:03,840 --> 01:51:06,800 PRESSURE OF 10 MERCURY IT'S 2100 01:51:06,800 --> 01:51:07,400 PHYSIOLOGICAL. 2101 01:51:07,400 --> 01:51:09,960 IF YOU ENHANCED CONTRACTION OF 2102 01:51:09,960 --> 01:51:10,960 THE STOMACH. 2103 01:51:10,960 --> 01:51:14,520 IF YOU INCREASE UP TO 20 MERCURY 2104 01:51:14,520 --> 01:51:17,800 AND YOU WILL DIS LAPSE THE 2105 01:51:17,800 --> 01:51:19,840 CONTRACTION AND MY IMPRESSION IS 2106 01:51:19,840 --> 01:51:22,080 THAT UNDER PHYSIOLOGICAL 2107 01:51:22,080 --> 01:51:23,840 CONDITIONS, SO THEN WE JUST HAVE 2108 01:51:23,840 --> 01:51:26,800 A NORMAL EARTH. 2109 01:51:26,800 --> 01:51:27,640 DON'T OVER EAT. 2110 01:51:27,640 --> 01:51:29,760 WHEN YOU OVER EAT YOU WILL FEEL 2111 01:51:29,760 --> 01:51:31,240 BLOAT AND PAIN. 2112 01:51:31,240 --> 01:51:33,080 SO WHEN YOU DISTANCE STOMACH TOO 2113 01:51:33,080 --> 01:51:35,080 MUCH, THEN YOU WILL GENERATE 2114 01:51:35,080 --> 01:51:38,320 PAIN AND UNDER THEIR CONDITION, 2115 01:51:38,320 --> 01:51:39,600 PROBABLY THE DOR SAL THE SIGNAL 2116 01:51:39,600 --> 01:51:42,320 WILL GO TO SYMPATHETIC PATHWAY 2117 01:51:42,320 --> 01:51:43,720 AND UNDER PHYSIOLOGICAL 2118 01:51:43,720 --> 01:51:45,120 CONDITIONS, MOST OF THE TIME, 2119 01:51:45,120 --> 01:51:47,000 SIGNAL WILL GO THROUGH THE VAGAL 2120 01:51:47,000 --> 01:51:50,640 PATHWAY BUT THAT'S NOT THE 100% 2121 01:51:50,640 --> 01:51:54,800 SO THERE'S BOTH PATHWAYS BUT 2122 01:51:54,800 --> 01:51:57,080 LOGICALLY, IT'S MORE VAGAL. 2123 01:51:57,080 --> 01:52:00,520 AND IT IS MORE SYMPATHETIC AND 2124 01:52:00,520 --> 01:52:06,320 ALSO, THE STOMACH HAS ADAPTATION 2125 01:52:06,320 --> 01:52:08,000 PROCESS SO WE HAVE TO BE CAREFUL 2126 01:52:08,000 --> 01:52:14,080 WHEN YOU DIS TENT THE STOMACH 2127 01:52:14,080 --> 01:52:15,520 BECAUSE WE RELAX AND YOUR 2128 01:52:15,520 --> 01:52:16,800 PRESSURE WILL DECREASE AND YOU 2129 01:52:16,800 --> 01:52:21,360 HAVE TO THINK WHETHER 10MAO OR 2130 01:52:21,360 --> 01:52:23,400 WITH 5MAO OR WHATEVER AT 2131 01:52:23,400 --> 01:52:24,520 BEGINNING THE PRESSURE IS HIGH 2132 01:52:24,520 --> 01:52:26,200 AND AFTERWARDS THE PRESSURE IS 2133 01:52:26,200 --> 01:52:26,440 GONE. 2134 01:52:26,440 --> 01:52:28,480 SO WE HAVE TO BE A LITTLE BIT 2135 01:52:28,480 --> 01:52:31,080 CAREFUL WHEN YOU DO DETENTION IF 2136 01:52:31,080 --> 01:52:35,840 IF YOU DO SMALL, IT'S EVEN MORE 2137 01:52:35,840 --> 01:52:36,920 COMPLICATED BECAUSE SMALL WILL 2138 01:52:36,920 --> 01:52:42,400 KEEP RELAXING AND THEN YOU CAN 2139 01:52:42,400 --> 01:52:44,280 KEEP PUSHING MORE AIR TO 2140 01:52:44,280 --> 01:52:48,720 MAINTAIN THE PRESSURE. 2141 01:52:48,720 --> 01:52:51,160 >>WE NEVER WENT ABOVE 2142 01:52:51,160 --> 01:52:52,840 10 MILLIGRAMS MERCURY BUT ALSO, 2143 01:52:52,840 --> 01:52:56,480 WE SEE THE SAME RESULTS IF WE 2144 01:52:56,480 --> 01:52:59,200 INDUCE RELAXATION WITH GOP1 SO 2145 01:52:59,200 --> 01:53:05,200 IT DOES NOT SEEM TO DEPEND ON 2146 01:53:05,200 --> 01:53:08,040 THE CONTRACTION OR GOING THE 2147 01:53:08,040 --> 01:53:08,480 PHYSIOLOGICAL RANGE. 2148 01:53:08,480 --> 01:53:10,800 >>ONE MORE QUICK QUESTION. 2149 01:53:10,800 --> 01:53:11,920 >>QUESTION. 2150 01:53:11,920 --> 01:53:13,280 I THINK THIS IS VERY INTERESTING 2151 01:53:13,280 --> 01:53:15,520 AND WE NEED TO BE A LITTLE BIT 2152 01:53:15,520 --> 01:53:16,560 MORE OPEN. 2153 01:53:16,560 --> 01:53:20,320 SO EVOLUTIONARILY, OF COURSE, 2154 01:53:20,320 --> 01:53:21,720 DRG SENSE INCEPTION ALL OVER THE 2155 01:53:21,720 --> 01:53:23,120 BODY AND IT DOESN'T MAKE SENSE 2156 01:53:23,120 --> 01:53:25,680 THAT IT'S JUST FOR MUSCLES. 2157 01:53:25,680 --> 01:53:28,480 AND THE RESULTS ARE THE LESION 2158 01:53:28,480 --> 01:53:31,520 ACTUALLY, IF IT WOULD BE PAIN, 2159 01:53:31,520 --> 01:53:35,520 YOU KNOW, OVER EATING, RIGHT, 2160 01:53:35,520 --> 01:53:38,160 YOU WOULD EXPECT THAT THEY 2161 01:53:38,160 --> 01:53:39,800 WOULDN'T BE NECESSARILY OVER 2162 01:53:39,800 --> 01:53:42,800 EATING AND IN THE CASE OF VAGUS, 2163 01:53:42,800 --> 01:53:44,800 SO MAYBE THEY'RE SIGNALING 2164 01:53:44,800 --> 01:53:47,440 DIFFERENT ASPECTS AND MECHANIC 2165 01:53:47,440 --> 01:53:50,120 SENSATION, I MEAN WE KNOW IT 2166 01:53:50,120 --> 01:53:58,320 EXISTS IN THE VRG TO SPINAL CORD 2167 01:53:58,320 --> 01:54:00,000 AND I'LL TALK IN THE END ABOUT 2168 01:54:00,000 --> 01:54:01,680 THE MOTOR ASPECT AND YOU WILL 2169 01:54:01,680 --> 01:54:06,600 SEE IT'S VERY SIMILAR WITH MOTOR 2170 01:54:06,600 --> 01:54:09,360 CORTEX INNOVATING INTERNAL 2171 01:54:09,360 --> 01:54:11,120 ORGANS SO MAYBE, UNLESS THERE'S 2172 01:54:11,120 --> 01:54:13,760 SOME TECHNICAL ISSUES WITH MY, 2173 01:54:13,760 --> 01:54:16,560 MAYBE WE'VE OVERLOOKED AND WE'VE 2174 01:54:16,560 --> 01:54:20,240 THOUGHT EVERYTHING IN TERMS OF 2175 01:54:20,240 --> 01:54:22,000 SENSING AND CONTROL THAT GOES 2176 01:54:22,000 --> 01:54:24,360 THROUGH THE CORD IS FOR OVERT 2177 01:54:24,360 --> 01:54:28,480 MOVEMENT BUT IT MAY BE FOR 2178 01:54:28,480 --> 01:54:28,760 PHYSIOLOGY. 2179 01:54:28,760 --> 01:54:30,600 >>WE NEED TO STOP HERE. 2180 01:54:30,600 --> 01:54:32,760 THERE ARE A FEW MORE QUESTIONS 2181 01:54:32,760 --> 01:54:34,160 AND MAYBE THOSE INDIVIDUALS, WE 2182 01:54:34,160 --> 01:54:37,160 CAN KIND OF PASS THAT ONTO THE 2183 01:54:37,160 --> 01:54:37,440 SPEAKERS. 2184 01:54:37,440 --> 01:54:39,080 SO GRATEFUL FOR THE LIVELY 2185 01:54:39,080 --> 01:54:39,400 DISCUSSION. 2186 01:54:39,400 --> 01:54:42,200 THANK YOU. 2187 01:54:42,200 --> 01:54:45,840 >>WE WILL HAVE A BRIEF BREAK. 2188 01:54:45,840 --> 01:54:47,600 IF YOU WANT TO GIVE UP AND MOVE 2189 01:54:47,600 --> 01:54:50,440 AROUND AND WE'LL BE BACK HERE AT 2190 01:54:50,440 --> 01:54:52,840 2:35 TO GET STARTED. 2191 01:54:52,840 --> 01:54:53,560 WELCOME BACK. 2192 01:54:53,560 --> 01:54:55,040 WE'LL STARTED WITH SESSION 2 AND 2193 01:54:55,040 --> 01:54:56,800 I'D LIKE TO GO AHEAD AND 2194 01:54:56,800 --> 01:54:58,120 INTRODUCE OUR SESSION 2 2195 01:54:58,120 --> 01:55:04,800 MODERATOR, Dr. MARK ANDERMANN. 2196 01:55:04,800 --> 01:55:07,040 >>WE'VE NOT EXCITING LINEUP FOR 2197 01:55:07,040 --> 01:55:09,000 THE SECOND SESSION HERE AND THE 2198 01:55:09,000 --> 01:55:11,520 SESSION IS ON PULMONARY CARD 2199 01:55:11,520 --> 01:55:13,080 VASCULAR SYSTEM AND BRAIN 2200 01:55:13,080 --> 01:55:16,800 CONNECTIONS AND THERE'S FOUR 2201 01:55:16,800 --> 01:55:18,440 SPEAKERS AND I'LL GOING TO READ 2202 01:55:18,440 --> 01:55:23,720 OUT THEIR TITLES AND NAMES IT'S 2203 01:55:23,720 --> 01:55:25,200 A 15-MINUTE TALK AT THE END 2204 01:55:25,200 --> 01:55:26,200 WE'LL HAVE 10 MINUTES FOR 2205 01:55:26,200 --> 01:55:29,240 QUESTIONS AND WE MIGHT REMEMBER 2206 01:55:29,240 --> 01:55:30,880 IF YOU END YOUR QUESTIONS 2207 01:55:30,880 --> 01:55:32,440 ON-LINE TO EXPLAIN WHICH SPEAKER 2208 01:55:32,440 --> 01:55:34,680 THE QUESTION IS DIRECTED TO. 2209 01:55:34,680 --> 01:55:37,000 SO, WE'RE GOING TO START WITH A 2210 01:55:37,000 --> 01:55:43,120 TALK BY Dr. XIN SUN FROM UCSD 2211 01:55:43,120 --> 01:55:44,320 DISSECT THE INTEROCEPTION KIRK 2212 01:55:44,320 --> 01:55:45,480 ET THAT CONTROLS AIRWAY AND 2213 01:55:45,480 --> 01:55:49,680 WE'LL HEAR FROM ARLIN BLOOD AND 2214 01:55:49,680 --> 01:55:52,080 CHRISTOPHER WILSON WITH 2215 01:55:52,080 --> 01:55:52,920 UNRAVELING LUNG INTEROCEPTION 2216 01:55:52,920 --> 01:55:54,480 AND ITS FUNCTIONAL CONSEQUENCE 2217 01:55:54,480 --> 01:55:57,640 IN THE DEVELOPING OWE VINE LUNG 2218 01:55:57,640 --> 01:55:59,800 AND DISSECT KNEW OWE CIRCUITS 2219 01:55:59,800 --> 01:56:05,040 FOR BREATHING PATTERNS AND Dr. 2220 01:56:05,040 --> 01:56:08,440 AJIJOLA FROM UCLA WILL TALK 2221 01:56:08,440 --> 01:56:12,680 ABOUT DEFINING SUBSETS OF SI 2222 01:56:12,680 --> 01:56:14,240 SYMPATHETIC NEURONS MEDIATING 2223 01:56:14,240 --> 01:56:15,640 CARDIAC NEURO TRANSMISSION. 2224 01:56:15,640 --> 01:56:16,320 WITH THAT I'LL PASS IT OVER. 2225 01:56:16,320 --> 01:56:22,320 I'D LIKE TO START BY THANKING 2226 01:56:22,320 --> 01:56:26,120 DAVID AND WEN AND THE NCCIH 2227 01:56:26,120 --> 01:56:27,320 LEADERSHIP FOR SUPPORTING THIS 2228 01:56:27,320 --> 01:56:28,960 WORK AND I'M HERE TO GIVE YOU A 2229 01:56:28,960 --> 01:56:34,000 PROGRESS REPORT OF OUR WORK ON 2230 01:56:34,000 --> 01:56:38,920 THE AIRWAY CIRCUITS. 2231 01:56:38,920 --> 01:56:40,520 SO SINCE I'M THE FIRST SPEAKER 2232 01:56:40,520 --> 01:56:43,080 IN THIS CARDIO PULMONARY SESSION 2233 01:56:43,080 --> 01:56:46,600 I'D LIKE TO START WITH THIS 2234 01:56:46,600 --> 01:56:48,560 SLIDE TO SAY THAT THE LUNG IS 2235 01:56:48,560 --> 01:56:50,320 NOT JUST A VITAL AND BEAUTIFUL 2236 01:56:50,320 --> 01:56:52,760 ORGAN BUT IT'S ALSO A BEAUTIFUL 2237 01:56:52,760 --> 01:56:55,880 ORGAN TO STUDY INTEROCEPTION AND 2238 01:56:55,880 --> 01:56:58,240 GIVEN IT'S HUGE SURFACE AREA AN 2239 01:56:58,240 --> 01:56:59,760 AVERAGE ADULT PERSON HAS ABOUT A 2240 01:56:59,760 --> 01:57:02,600 HALF A SIZE OF A TENNIS COURT 2241 01:57:02,600 --> 01:57:05,560 PACKED INTO OUR CHEST AND IN 2242 01:57:05,560 --> 01:57:07,240 ADDITION, AN AVERAGE PERSON 2243 01:57:07,240 --> 01:57:08,880 RESTING FIVE TO EIGHT LITERS OF 2244 01:57:08,880 --> 01:57:12,200 AIR THAT COMES IN AND OUT OF OUR 2245 01:57:12,200 --> 01:57:12,600 LUNGS. 2246 01:57:12,600 --> 01:57:14,920 SO THIS AIR CAN CONTAIN A 2247 01:57:14,920 --> 01:57:17,280 DIVERSITY OF SIGNALS INCLUDING 2248 01:57:17,280 --> 01:57:18,720 ALLERGANS, POLLUTANTS, INCREASE 2249 01:57:18,720 --> 01:57:21,880 AND DECREASING OXYGEN AND ALSO A 2250 01:57:21,880 --> 01:57:29,720 DIFFERENT SYSTEM MECHANICAL 2251 01:57:29,720 --> 01:57:30,440 TENSION. 2252 01:57:30,440 --> 01:57:34,200 THE LUNG IS A BEAUTIFUL ORGAN TO 2253 01:57:34,200 --> 01:57:37,760 STUDY THE INTEROCEPTION 2254 01:57:37,760 --> 01:57:38,000 CIRCUITS. 2255 01:57:38,000 --> 01:57:38,560 I'M TRAINED DEVELOPMENTAL 2256 01:57:38,560 --> 01:57:41,520 BIOLOGY STUDIED SO I'LL ENTRY 2257 01:57:41,520 --> 01:57:44,000 POINT INTO STUDY THE LUNG STARTS 2258 01:57:44,000 --> 01:57:47,760 WITH ANATOMICAL MAPPING SO THIS 2259 01:57:47,760 --> 01:57:51,600 IS A WHOLE MOUSE LUNG CLEARED AN 2260 01:57:51,600 --> 01:57:53,360 IMAGED WITH THE SENSORY NERVES 2261 01:57:53,360 --> 01:57:55,120 THAT RUNS ALONG MOST OF THE 2262 01:57:55,120 --> 01:57:59,000 AIRWAYS THAT REACHES DEEP INTO 2263 01:57:59,000 --> 01:58:00,120 THE LUNG. 2264 01:58:00,120 --> 01:58:02,640 SO WE USED TO ADDRESS WHERE THE 2265 01:58:02,640 --> 01:58:04,520 SENSORY NERVES, THE CELL BODIES 2266 01:58:04,520 --> 01:58:06,280 AS WELL AS THEIR UPWARDS 2267 01:58:06,280 --> 01:58:08,360 PROJECTIONS INTO THE BRAIN STEM 2268 01:58:08,360 --> 01:58:11,160 WHEN USED THE GRADE APPROACHED 2269 01:58:11,160 --> 01:58:13,400 SOME OF THE ALREADY MENTIONED IN 2270 01:58:13,400 --> 01:58:14,880 THE FIRST SESSION, THE 2271 01:58:14,880 --> 01:58:17,960 RETROGRADE AAV AND WE HAVE USED 2272 01:58:17,960 --> 01:58:20,000 IT INTO THE LUNGS SO WE GET 2273 01:58:20,000 --> 01:58:23,640 WIDESPREAD INFECTION IN THE LUNG 2274 01:58:23,640 --> 01:58:25,760 INCLUDING IN THE NERVE TERMINALS 2275 01:58:25,760 --> 01:58:27,960 AND MOST OF THE CELL BODIES ARE 2276 01:58:27,960 --> 01:58:31,160 IN THE VAGAL GANGLIA AND WITH 2277 01:58:31,160 --> 01:58:33,440 VERY FEW NEURONS LABELED IN THE 2278 01:58:33,440 --> 01:58:36,520 DRG AND SO THE UPWARD PROJECTION 2279 01:58:36,520 --> 01:58:37,800 GOES INTO THE BRAIN STEM AND 2280 01:58:37,800 --> 01:58:39,320 THIS IS THE WHOLE BRAIN STEM 2281 01:58:39,320 --> 01:58:41,040 CLEARED AND AS YOU CAN SEE HERE 2282 01:58:41,040 --> 01:58:42,560 NOT SURPRISINGLY MOST OF THE 2283 01:58:42,560 --> 01:58:46,440 PROJECTIONS GOES TO THE NTS 2284 01:58:46,440 --> 01:58:48,000 REGION. 2285 01:58:48,000 --> 01:58:51,160 SO, WITH THIS SET UP, WE ASKED 2286 01:58:51,160 --> 01:58:53,280 WHAT ARE THE SPECIFIC SIGNALS 2287 01:58:53,280 --> 01:58:54,240 TRANSMITTED FROM THE LUNGS SO 2288 01:58:54,240 --> 01:58:59,840 THE FIRST SIGNAL WE LOOKED AT IS 2289 01:58:59,840 --> 01:59:00,280 ALLERGANS. 2290 01:59:00,280 --> 01:59:00,640 WHY? 2291 01:59:00,640 --> 01:59:03,280 IT'S A COMMON INHALED IRRITANT 2292 01:59:03,280 --> 01:59:05,560 COMING INTO THE LUNG AND IT 2293 01:59:05,560 --> 01:59:07,920 INDUCES SEVERAL TYPES OF 2294 01:59:07,920 --> 01:59:11,040 ADAPTIVE RESPONSES INCLUDING 2295 01:59:11,040 --> 01:59:13,160 AIRWAY CONSTRICTION, A TH2 2296 01:59:13,160 --> 01:59:18,480 IMMUNE INFILTRATION RESPONSE AS 2297 01:59:18,480 --> 01:59:23,600 WELL AS META PLAY SHA IN THE 2298 01:59:23,600 --> 01:59:34,200 AIRWAY AND IT'S EXCITING TO STUY 2299 01:59:35,840 --> 01:59:36,480 ALLERGEN RESPONSE BECAUSE AS 2300 01:59:36,480 --> 01:59:38,320 SHOWN HERE, IT'S AN IDEAL 2301 01:59:38,320 --> 01:59:41,120 SETTING TO LOOK AT NERVE, THE 2302 01:59:41,120 --> 01:59:43,320 PINK CELLS ARE IMMUNE CELLS AS 2303 01:59:43,320 --> 01:59:47,360 WELL AS LUNG SENSORY CELL TYPES 2304 01:59:47,360 --> 01:59:51,080 AND SENSORY CELL TYPES THE 2305 01:59:51,080 --> 01:59:52,280 ENDOCRINE CELLS HIGHLIGHTED HERE 2306 01:59:52,280 --> 01:59:54,600 AND INNOVATED BEAUTIFULLY BY 2307 01:59:54,600 --> 02:00:01,160 NERVES AND SO THESE NEURON 2308 02:00:01,160 --> 02:00:04,240 ENDOCRINE CELLS MENTIONED IN THE 2309 02:00:04,240 --> 02:00:05,880 FIRST TALK ARE WIRED BY NERVES 2310 02:00:05,880 --> 02:00:09,120 AS WELL AS THERE ARE IMMENSELY 2311 02:00:09,120 --> 02:00:10,480 SENSITIVE TO ALLERGAN RESPONSE 2312 02:00:10,480 --> 02:00:12,360 AND REALLY IMPORTANT FOR 2313 02:00:12,360 --> 02:00:18,400 TRANSMITTING THAT RESPONSE. 2314 02:00:18,400 --> 02:00:19,800 ALLERGAN RESPONSE IS DISEASE 2315 02:00:19,800 --> 02:00:21,440 RELEVANT IN PARTICULAR, ASTHMA 2316 02:00:21,440 --> 02:00:22,960 BEING A DISEASE THAT IS 2317 02:00:22,960 --> 02:00:27,480 TRIGGERED BY CHRONIC ALLERGAN 2318 02:00:27,480 --> 02:00:27,760 EXPOSURE. 2319 02:00:27,760 --> 02:00:30,680 SO TO STUDY ALLERGAN RESPONSE, I 2320 02:00:30,680 --> 02:00:32,720 MENTIONED THAT SINCE THE LUNG 2321 02:00:32,720 --> 02:00:34,400 INNOVATING SENSORY NERVE MOSTLY 2322 02:00:34,400 --> 02:00:37,520 PROJECT TO THE NTS REGION, WE'VE 2323 02:00:37,520 --> 02:00:40,680 USED FOUR-DOSE HOUSE DUST MIGHT 2324 02:00:40,680 --> 02:00:42,920 ALLERGY INDEX REGIME THAT IS 2325 02:00:42,920 --> 02:00:44,120 COMMONLY USED IN THE LUNG TO 2326 02:00:44,120 --> 02:00:46,920 STUDY ALLERGY RESPONSE AND 2327 02:00:46,920 --> 02:00:50,240 ADDRESSED THE NEURONAL 2328 02:00:50,240 --> 02:00:52,440 ACTIVATION IN THE NTS REGION YOU 2329 02:00:52,440 --> 02:00:54,760 CAN SEE HERE THERE'S A 2330 02:00:54,760 --> 02:00:56,080 BEAUTIFULLY STATISTICALLY 2331 02:00:56,080 --> 02:00:58,920 SIGNIFICANT INCREASE OF NEURON 2332 02:00:58,920 --> 02:01:00,560 TIVE TAIZATION IN THE THE NTS 2333 02:01:00,560 --> 02:01:07,080 REGION AND I WANT TO POINT OUT, 2334 02:01:07,080 --> 02:01:08,160 THIS IS RESPONSE HAPPENING AFTER 2335 02:01:08,160 --> 02:01:10,120 FOUR DOSES OF ALLERGAN CHALLENGE 2336 02:01:10,120 --> 02:01:11,320 AND IT'S NOT SEEING WITH THE 2337 02:01:11,320 --> 02:01:15,160 EARLY ADULTS SUGGESTING THAT 2338 02:01:15,160 --> 02:01:16,600 THERE'S A CHALLENGE AND 2339 02:01:16,600 --> 02:01:18,000 POTENTIAL PLASTICITY BUILT INTO 2340 02:01:18,000 --> 02:01:28,200 THE SYSTEM. 2341 02:01:42,680 --> 02:01:44,560 SO THE NEXT QUESTION IS WHICH 2342 02:01:44,560 --> 02:01:46,880 SUBSET OF THE NTS NEURONS MUTATE 2343 02:01:46,880 --> 02:01:48,520 IN THIS RESPONSE AS MANY OF YOU 2344 02:01:48,520 --> 02:01:52,760 STUDIED THE NTS FOR AN 2345 02:01:52,760 --> 02:01:54,120 INTEGRATING CENTER FOR MULTIPLE 2346 02:01:54,120 --> 02:01:57,280 ORGANS SO WE DID SINGLE NUCLEUS 2347 02:01:57,280 --> 02:01:59,120 BOTH AT THE BASELINE AS WELL AS 2348 02:01:59,120 --> 02:02:00,600 AFTER ALLERGAN CHALLENGE AND IN 2349 02:02:00,600 --> 02:02:03,560 BOTH SETTINGS, THE NTS NEURONS 2350 02:02:03,560 --> 02:02:04,640 SEGREGATE INTO CERTAIN CLUSTERS 2351 02:02:04,640 --> 02:02:08,400 IN OUR HANDS AND ALONG THOSE 2352 02:02:08,400 --> 02:02:10,160 CLUSTERS WE FOUND ONE OF THIS 2353 02:02:10,160 --> 02:02:15,280 CLUSTER MARKED BY THE DBH AS A 2354 02:02:15,280 --> 02:02:20,480 MARKER, IS SELECTIVELY ENRICHED 2355 02:02:20,480 --> 02:02:21,560 BY RESPONSE TIVE NOOSE OWNS AND 2356 02:02:21,560 --> 02:02:30,000 NEURONS.SO THE NEXT QUESTION WIN 2357 02:02:30,000 --> 02:02:31,960 ADDRESSED ARE THESE POSITIVE 2358 02:02:31,960 --> 02:02:34,800 NEURONS DBH FOR TRANSMITTING THE 2359 02:02:34,800 --> 02:02:36,840 ALLERGAN RESPONSE DOWNSTREAM? 2360 02:02:36,840 --> 02:02:38,840 SO TO DO THIS, WE USED THREE 2361 02:02:38,840 --> 02:02:42,600 DIFFERENT APPROACHES AND FIRST A 2362 02:02:42,600 --> 02:02:44,480 TOXIN TO ABATE THE POSITIVE 2363 02:02:44,480 --> 02:02:46,360 NEURONS AND SECOND WE USED THE 2364 02:02:46,360 --> 02:02:48,720 DTR SYSTEM IN COMBINATION WITH 2365 02:02:48,720 --> 02:02:56,760 THE DBH SPECIFIC THE THIRD ONE I 2366 02:02:56,760 --> 02:03:00,520 WILL SHOW YOU DATA FOR THE DREDD 2367 02:03:00,520 --> 02:03:01,840 SYSTEM WHICH WHEN WE INFECTED 2368 02:03:01,840 --> 02:03:06,560 THE AAV CARRYING THE FLEX INHIB 2369 02:03:06,560 --> 02:03:09,760 TREE VIRUS INTO THE NTS REGION 2370 02:03:09,760 --> 02:03:12,760 AND SO WITH THE INHIBITION OF 2371 02:03:12,760 --> 02:03:15,720 THOSE NEURONS IN THE PRESENCE OF 2372 02:03:15,720 --> 02:03:18,000 HDM WE FOUND IS THAT NEITHER OF 2373 02:03:18,000 --> 02:03:22,840 THE IMMUNE RESPONSE CELLS ARE 2374 02:03:22,840 --> 02:03:24,920 EFFECTED BUT THE AIRWAY 2375 02:03:24,920 --> 02:03:28,760 CONSTRICTION RESPONSE AND THE 2376 02:03:28,760 --> 02:03:33,560 MAJOR RESPONSE THAT BLOCKS AIR 2377 02:03:33,560 --> 02:03:34,880 FLOW IS EFFECTED SO BEFORE I 2378 02:03:34,880 --> 02:03:36,320 SHOW YOU THAT AND TELL YOU THAT 2379 02:03:36,320 --> 02:03:39,320 RESULT I WANT TO TELL YOU HOW WE 2380 02:03:39,320 --> 02:03:40,560 ESSAY FOR AIRWAY CONSTRICTION SO 2381 02:03:40,560 --> 02:03:46,240 WE USED A SYSTEM CALLED TO FOR 2382 02:03:46,240 --> 02:03:50,120 AIR FLOW AND THROUGH THE AIRWAY 2383 02:03:50,120 --> 02:03:53,120 AND THIS IS AFTER THE HDM 2384 02:03:53,120 --> 02:03:55,360 CHALLENGE SHOWN IN BOTH OF THESE 2385 02:03:55,360 --> 02:03:59,920 MEASUREMENTS AND SIMILAR 2386 02:03:59,920 --> 02:04:00,560 MEASUREMENTS FOR AIRWAY RESPONSE 2387 02:04:00,560 --> 02:04:02,120 SHOWN ON THE TOP ORANGE LINE 2388 02:04:02,120 --> 02:04:04,880 HERE IS AN ANIMAL AFTER THE 2389 02:04:04,880 --> 02:04:06,880 ALLERGAN CHALLENGE AND THIS 2390 02:04:06,880 --> 02:04:10,040 LEADS TO A PRODUCT ADAPTER SONS 2391 02:04:10,040 --> 02:04:11,720 TO THE CIRCUIT AS WELL AS THE 2392 02:04:11,720 --> 02:04:16,040 AIRWAY SMAIR SMOOTH MUSCLE SO WN 2393 02:04:16,040 --> 02:04:24,120 WITH ACUTE MESSAGE THAT ACUTELY 2394 02:04:24,120 --> 02:04:25,880 CONSTRICTS THE AIRWAY SO YOU SEE 2395 02:04:25,880 --> 02:04:28,600 THE EXACERBATED RESPONSE TO 2396 02:04:28,600 --> 02:04:30,000 AIRWAY CONSTRICTION COMPARED TO 2397 02:04:30,000 --> 02:04:31,040 THE SALINE CONTROL SO THIS IS 2398 02:04:31,040 --> 02:04:32,520 SIMILAR TO WHAT HAPPENS TO 2399 02:04:32,520 --> 02:04:35,280 ASMATIC PATIENTS YOU GET 2400 02:04:35,280 --> 02:04:36,240 EXACERBATED RESPONSE. 2401 02:04:36,240 --> 02:04:39,640 SO THIS IS HOW WE ASSAY FOR IT 2402 02:04:39,640 --> 02:04:42,720 AND WHEN WE HAVE THE DREDD 2403 02:04:42,720 --> 02:04:46,160 SYSTEM COMPARED TO CNL OR 2404 02:04:46,160 --> 02:04:49,760 WITHOUT IT SO WITH THE CNO 2405 02:04:49,760 --> 02:04:53,720 STIMULATION OF THE INHIBITORY 2406 02:04:53,720 --> 02:04:55,240 DREDD, WE VERY MUCH BLUNTED THAT 2407 02:04:55,240 --> 02:04:58,520 HYPER REACTIVITY RESPONSE 2408 02:04:58,520 --> 02:04:59,800 COMPARED TO THE CONTROL 2409 02:04:59,800 --> 02:05:02,840 SUGGESTING THE NTH NEURON 2410 02:05:02,840 --> 02:05:05,240 ACTIVATION IS NECESSARY FOR A 2411 02:05:05,240 --> 02:05:09,760 HYPER REACTIVITY RESPONSE. 2412 02:05:09,760 --> 02:05:11,720 WHAT WILL THE FLIP SIDE? 2413 02:05:11,720 --> 02:05:15,040 WE USE THE ACTIVATION DREDD 2414 02:05:15,040 --> 02:05:25,520 SYSTEM INJECTED INTO THE AND 2415 02:06:02,360 --> 02:06:12,800 THEY DIRECTLY INNOVATE THE -- 2416 02:06:24,720 --> 02:06:27,400 >>THEY ARE INNOVATED BY NERVE 2417 02:06:27,400 --> 02:06:37,880 TERMINALS AND IT'S THESE AND 2418 02:06:40,720 --> 02:06:42,200 CONSTRICTION. 2419 02:06:42,200 --> 02:06:44,360 SO, WITH THIS NEURO MAP WE KNOW 2420 02:06:44,360 --> 02:06:47,320 THAT IT'S PART OF THE PATHWAY SO 2421 02:06:47,320 --> 02:06:50,040 OUR THE NEURONS REQUIRED FOR THE 2422 02:06:50,040 --> 02:06:51,560 ALLERGAN RESPONSE AND SO HERE, 2423 02:06:51,560 --> 02:06:53,880 USING THE INHIB TREE DREAD AS 2424 02:06:53,880 --> 02:06:56,240 WELL AS THE ACTIVATION DREDD WE 2425 02:06:56,240 --> 02:06:58,520 SHOWED THAT LIKE THE NTS 2426 02:06:58,520 --> 02:07:00,760 DEVIATION NEURONS THE NA NEURONS 2427 02:07:00,760 --> 02:07:03,280 ARE NECESSARY AND STUFF FOR 2428 02:07:03,280 --> 02:07:05,600 ALLERGAN INDUCED AREA HYPER 2429 02:07:05,600 --> 02:07:07,480 ACTIVITY SO THE FINAL DATA SITE 2430 02:07:07,480 --> 02:07:09,160 I'M GOING TO SHOW YOU ABOUT IS 2431 02:07:09,160 --> 02:07:13,560 TO GET TO THE SIGNAL OF 2432 02:07:13,560 --> 02:07:18,280 TRANSMISSION AND IT'S A VERY 2433 02:07:18,280 --> 02:07:23,440 SMALL CLUSTER OF NEURONS AND 2434 02:07:23,440 --> 02:07:25,080 THEY CLUSTER OUT TO THREE 2435 02:07:25,080 --> 02:07:27,320 DIFFERENT SUB TYPES AND WE CAN 2436 02:07:27,320 --> 02:07:29,680 THEN LOOK AT RECEPTORS PAIRING 2437 02:07:29,680 --> 02:07:31,920 WITH THOSE DIFFERENT NODES AND 2438 02:07:31,920 --> 02:07:33,560 FROM THOSE INFORMATION WE 2439 02:07:33,560 --> 02:07:35,760 HYPOTHESIZED THAT THE DBH 2440 02:07:35,760 --> 02:07:38,360 NEURONS MIGHT ACT AS CAPABLE OF 2441 02:07:38,360 --> 02:07:39,960 PRODUCING NOR EPINEPHRIN WITH 2442 02:07:39,960 --> 02:07:41,200 THE RECEPTORS OF BEING PRESENT 2443 02:07:41,200 --> 02:07:47,080 IN THE NEURONS SO THAT MIGHT BE 2444 02:07:47,080 --> 02:07:48,760 A TRANSMITTER AND WHAT WE DID IS 2445 02:07:48,760 --> 02:07:51,160 TO COME IN AND INFUSE INTO THE 2446 02:07:51,160 --> 02:07:54,480 NA REGION SPECIFICALLY 2447 02:07:54,480 --> 02:08:05,080 ANTAGONIST FOR THE AND SO WITH T 2448 02:08:55,960 --> 02:09:04,240 I'D LIKE TO THANK AND IT'S 2449 02:09:04,240 --> 02:09:05,240 SPEARHEADED THIS WORK AND I'M 2450 02:09:05,240 --> 02:09:07,760 VERY GRATEFUL FOR MY FUNDING AND 2451 02:09:07,760 --> 02:09:10,400 VERY GRATEFUL FOR OUR NEWER OLE 2452 02:09:10,400 --> 02:09:12,680 BIOLOGIST COLLABORATORS. 2453 02:09:12,680 --> 02:09:12,960 THANK YOU. 2454 02:09:12,960 --> 02:09:16,640 [APPLAUSE] 2455 02:09:16,640 --> 02:09:17,800 THANK YOU, VERY MUCH. 2456 02:09:17,800 --> 02:09:21,680 OK, WE HAVE TIME FOR ONE QUICK 2457 02:09:21,680 --> 02:09:22,000 QUESTION. 2458 02:09:22,000 --> 02:09:26,000 I THINK THE SECOND PERSON FROM 2459 02:09:26,000 --> 02:09:34,320 THE END. 2460 02:09:34,320 --> 02:09:35,160 CONGRATULATIONS. 2461 02:09:35,160 --> 02:09:37,520 SO, YOU MENTIONED THE DBH 2462 02:09:37,520 --> 02:09:48,040 NEURONS IN THE HYPER SENSITIVE 2463 02:10:00,320 --> 02:10:01,840 >>I HAVEN'T DONE THAT PART OF 2464 02:10:01,840 --> 02:10:03,240 THE CONTROL FOR GETTING WHEN WE 2465 02:10:03,240 --> 02:10:05,440 DID MANIPULATE THE NA REGION WE 2466 02:10:05,440 --> 02:10:06,840 LOOKED AT THE BRAIN CONTROL AND 2467 02:10:06,840 --> 02:10:07,680 THE BASELINE. 2468 02:10:07,680 --> 02:10:08,880 WE DID NOT SEE AN EFFECT. 2469 02:10:08,880 --> 02:10:09,880 >>I SEE. 2470 02:10:09,880 --> 02:10:10,560 THANK YOU. 2471 02:10:10,560 --> 02:10:12,720 >>THAT'S AN IMPORTANT QUESTION. 2472 02:10:12,720 --> 02:10:15,680 THANK YOU. 2473 02:10:15,680 --> 02:10:18,080 >>LET'S MOVE ON TO THE NEXT 2474 02:10:18,080 --> 02:10:18,440 SPEAKER. 2475 02:11:09,840 --> 02:11:11,560 >>THERE'S A INTER PLAY BETWEEN 2476 02:11:11,560 --> 02:11:21,800 THE BRAIN AND. 2477 02:11:54,720 --> 02:11:56,520 >>WE WANT TO DETERMINE WHETHER 2478 02:11:56,520 --> 02:11:58,040 OR NOT TRAFFIC CHANGES IN THE 2479 02:11:58,040 --> 02:12:01,120 VAGUS DURING THE COURSE OF 2480 02:12:01,120 --> 02:12:03,200 DEVELOPMENT SO WE HAVE -- WE CAN 2481 02:12:03,200 --> 02:12:05,080 IMPLANT AND WE DID INVASIVE 2482 02:12:05,080 --> 02:12:15,400 MEASUREMENTS JUST. 2483 02:16:12,440 --> 02:16:13,280 >>SHORTLY AFTER BIRTH. 2484 02:16:13,280 --> 02:16:15,120 WE'RE LOOKING AT THE FUNCTIONAL 2485 02:16:15,120 --> 02:16:17,880 EFFECTS OF THE VAGUS NERVE AND 2486 02:16:17,880 --> 02:16:20,720 HOW IT ORCHESTRATES THE 2487 02:16:20,720 --> 02:16:21,680 CARDIOVASCULAR TRANSLATION THAT 2488 02:16:21,680 --> 02:16:25,240 HAPPENS AT BIRTH SO WE WILL AN 2489 02:16:25,240 --> 02:16:28,400 EARLY STAGE ABOUT 100 DAYS IN 2490 02:16:28,400 --> 02:16:30,320 GESTATION AND LET THEM PRE GRES 2491 02:16:30,320 --> 02:16:32,640 TO THE TERM AND DO A C-SECTION 2492 02:16:32,640 --> 02:16:34,920 WHILE WE MEASURE CARDIO 2493 02:16:34,920 --> 02:16:36,320 PULMONARY PARAMETERS AND THIS 2494 02:16:36,320 --> 02:16:38,800 WAS KIND OF TYPICAL RESPONSE TO 2495 02:16:38,800 --> 02:16:42,120 BIRTH FOR A HUGE INCREASE IN 2496 02:16:42,120 --> 02:16:43,440 PULMONARY BLOOD FLOW AND A 2497 02:16:43,440 --> 02:16:47,040 DECREASE IN RESISTANCE AND BLOOD 2498 02:16:47,040 --> 02:16:49,200 FLOW WE CAN MEASURE SO WE'LL 2499 02:16:49,200 --> 02:16:52,680 INSTRUMENT THE ANIMAL TO MEASURE 2500 02:16:52,680 --> 02:16:53,840 THESE AND TREASURE AND GO 2501 02:16:53,840 --> 02:16:56,200 THROUGH A C-SECTION AND 2502 02:16:56,200 --> 02:16:57,600 FOLLOWING THIS PROTOCOL AND 2503 02:16:57,600 --> 02:17:00,720 WE'LL SUBJECT THEM TO A HYPOXIC 2504 02:17:00,720 --> 02:17:03,840 STIMULUS AND WATCH THE LUNGS AND 2505 02:17:03,840 --> 02:17:04,960 BASAL CONSTRICT AGAINST THE 2506 02:17:04,960 --> 02:17:06,360 HYPOXIA AND WATCH THE HEART RATE 2507 02:17:06,360 --> 02:17:07,720 RESPONSE AND THIS IS DONE IN 2508 02:17:07,720 --> 02:17:09,360 ANIMALS THAT HAVE A VAGUS 2509 02:17:09,360 --> 02:17:11,520 COMPARED THAT THOSE HAVE BEEN 2510 02:17:11,520 --> 02:17:14,640 DENERVATED TO SEE HOW THEY 2511 02:17:14,640 --> 02:17:15,360 RESPOND. 2512 02:17:15,360 --> 02:17:17,840 SOME PRELIMINARY DATA, NOT TOO 2513 02:17:17,840 --> 02:17:19,840 SURPRISING, IF THEY ARE 2514 02:17:19,840 --> 02:17:20,560 DEINNERVATED ANIMALS THEY COME 2515 02:17:20,560 --> 02:17:22,680 IN WITH A RESTING HEART RATE 2516 02:17:22,680 --> 02:17:25,880 THAT IS HIGHER THAN OUR SHAM 2517 02:17:25,880 --> 02:17:29,200 CONTROL ANIMALS AND THIS IS AN 2518 02:17:29,200 --> 02:17:30,800 PROJECT BUT THIS IS 2519 02:17:30,800 --> 02:17:33,920 REPRESENTATIVE OF 30 OR 40 2520 02:17:33,920 --> 02:17:36,320 ANIMALS WE'VE DONE WITH THIS 2521 02:17:36,320 --> 02:17:37,360 PROTOCOL. 2522 02:17:37,360 --> 02:17:39,680 PULMONARY VASCULAR RESISTANCE IS 2523 02:17:39,680 --> 02:17:41,480 ELEVATED IN THE THROW ANIMALS 2524 02:17:41,480 --> 02:17:43,200 THAT WE'VE DEINNERVATED AND 2525 02:17:43,200 --> 02:17:44,720 STUDIED SO FAR SO WE'LL FOCUS ON 2526 02:17:44,720 --> 02:17:47,480 HOW INNERRIZATION OF THE 2527 02:17:47,480 --> 02:17:50,040 PULMONARY MIGHT BE CHANGED BY 2528 02:17:50,040 --> 02:17:52,440 THIS AND PULMONARY COMPLIANCE IS 2529 02:17:52,440 --> 02:17:54,240 DECREASED IN OUR DENERVATED 2530 02:17:54,240 --> 02:17:58,680 ANIMALS AND THIS IS WHAT A PRE 2531 02:17:58,680 --> 02:18:04,400 TERM WOULD LOOK LIKE AND THESE 2532 02:18:04,400 --> 02:18:05,040 ARE TERM LAMBS. 2533 02:18:05,040 --> 02:18:07,120 I'LL TURN IT OVER TO Dr. 2534 02:18:07,120 --> 02:18:11,360 WILSON TO TALK. 2535 02:18:11,360 --> 02:18:15,880 >>SO IT'S FOCUSED ON A MORE 2536 02:18:15,880 --> 02:18:19,400 SIGNAL THEORY KIND OF APPROACH 2537 02:18:19,400 --> 02:18:21,000 TO VAGUS NERVE AND THE OTHER WAY 2538 02:18:21,000 --> 02:18:23,120 AROUND, CNS TO THE LUNG SINCE WE 2539 02:18:23,120 --> 02:18:26,960 GET TWO FOR TREE THERE. 2540 02:18:26,960 --> 02:18:28,080 DURING GESTATION OF BIRTH IN THE 2541 02:18:28,080 --> 02:18:31,600 SENSE WE'RE USING LONG-TERM 2542 02:18:31,600 --> 02:18:32,440 RECORDINGS THAT WE HAVE HOOKED 2543 02:18:32,440 --> 02:18:33,880 UP TO A RADIO SYSTEM. 2544 02:18:33,880 --> 02:18:36,200 IF YOU LOOK AT THE IMPLANT HERE, 2545 02:18:36,200 --> 02:18:38,240 ABOUT 95 DAYS OF GESTATION WE 2546 02:18:38,240 --> 02:18:41,160 CAN DO RECORDINGS OUT TO 150 2547 02:18:41,160 --> 02:18:42,280 DAYS WHICH IS TERM. 2548 02:18:42,280 --> 02:18:45,000 NORMALLY WHEN WE THINK ABOUT 2549 02:18:45,000 --> 02:18:46,400 PHYSIOLOGICAL WINDOWS WE TAKE 2550 02:18:46,400 --> 02:18:47,880 SNAPSHOTS JUST LIKE STOP-MOTION 2551 02:18:47,880 --> 02:18:49,200 ANIMATION WHERE WE GET LITTLE 2552 02:18:49,200 --> 02:18:50,480 WINDOWS OF PHYSIOLOGICAL 2553 02:18:50,480 --> 02:18:52,200 ACTIVITY BUT NOW WE'RE ABLE TO 2554 02:18:52,200 --> 02:18:53,560 DO LONG-TERM RECORDING AND 2555 02:18:53,560 --> 02:18:55,760 INDUCE SIGNAL ANALYSIS ON THAT 2556 02:18:55,760 --> 02:18:57,480 PARTICULAR SIGNAL AND WE GET ECG 2557 02:18:57,480 --> 02:19:01,720 SO WE HAVE ECG AS WELL AS VAGUS 2558 02:19:01,720 --> 02:19:03,760 ACTIVITY SO WE CAN CROSS 2559 02:19:03,760 --> 02:19:07,400 CORRELATION OF ECG AND VAGUS 2560 02:19:07,400 --> 02:19:08,360 NERVE ACTIVITY AND WE CAN LOOK 2561 02:19:08,360 --> 02:19:10,120 AT HEART RATE VARIABILITIES 2562 02:19:10,120 --> 02:19:15,440 METRICS BASED ON SDNN, SDANN, 2563 02:19:15,440 --> 02:19:17,360 NM50 AND LOOK AT FREQUENCY SEW 2564 02:19:17,360 --> 02:19:20,600 MAIN ANALYSIS USING FAT FORWARD 2565 02:19:20,600 --> 02:19:22,480 TRANSFORMS WITH TIME VARIANT AND 2566 02:19:22,480 --> 02:19:24,120 INFRASTRUCTURE RACE ANALYSIS AND 2567 02:19:24,120 --> 02:19:28,080 ANY OF THOSE THINGS AND ON THESE 2568 02:19:28,080 --> 02:19:28,560 SIGNALS. 2569 02:19:28,560 --> 02:19:30,600 IT ALLOWS TO LOOK AT BALANCE AS 2570 02:19:30,600 --> 02:19:34,840 WELL AND OUR DATA ANALYSIS TOOLS 2571 02:19:34,840 --> 02:19:38,240 STACK IS PYTHON, NON PYTHON AND 2572 02:19:38,240 --> 02:19:38,840 JUPYTER NOTEBOOKS THAT LITTLE 2573 02:19:38,840 --> 02:19:42,280 SCRABBLE AAVAILABLE TO EVERYONE. 2574 02:19:42,280 --> 02:19:44,080 SO HERE IS JUST AN EXAMPLE OF 2575 02:19:44,080 --> 02:19:44,960 SOME OF OUR PRELIMINARY DATA, 2576 02:19:44,960 --> 02:19:47,160 THIS WAS ACQUIRED WITH HOOK 2577 02:19:47,160 --> 02:19:50,400 ELECTRODES NOT OUR NEW CUFF 2578 02:19:50,400 --> 02:19:51,280 ELECTRODES. 2579 02:19:51,280 --> 02:19:56,520 HERE IS AN FFT OF THE VAGUS 2580 02:19:56,520 --> 02:19:59,320 NERVE ACTIVITY, WE SEE IN B AND 2581 02:19:59,320 --> 02:20:01,280 TIME SPECTRUM OVER MULTIPLE 2582 02:20:01,280 --> 02:20:02,440 MINUTES HERE SO WE'RE JUST AT 2583 02:20:02,440 --> 02:20:04,240 THE BEGINNING OF DOING THIS 2584 02:20:04,240 --> 02:20:05,960 ANALYSIS IN THE SMALL NUMBER OF 2585 02:20:05,960 --> 02:20:07,440 ANIMALS THAT WE'VE RECORDED DATA 2586 02:20:07,440 --> 02:20:11,480 FROM BUT WE HAVE SOME OF THAT 2587 02:20:11,480 --> 02:20:11,800 DATA. 2588 02:20:11,800 --> 02:20:13,120 NOW I'M JUST GOING TO SUMMARIZE 2589 02:20:13,120 --> 02:20:14,320 A FEW OF THE ARE 2590 02:20:14,320 --> 02:20:16,800 GOING ON WITH THE PROJECT AND 2591 02:20:16,800 --> 02:20:27,360 SOME OF THE -- WE'RE HONORED TO 2592 02:21:12,440 --> 02:21:14,760 COLLABORATE WITH HER AND DENISE 2593 02:21:14,760 --> 02:21:17,040 AND JAMIE WORKS WITH Dr. SUN 2594 02:21:17,040 --> 02:21:18,640 AND OUR POSTDOC WHO IS DOING A 2595 02:21:18,640 --> 02:21:24,080 HUGE AMOUNT OF THE WORK IS 2596 02:21:24,080 --> 02:21:26,080 KARINA MAYAGOLITA WHO WORKS WITH 2597 02:21:26,080 --> 02:21:27,120 US AT LLU. 2598 02:21:27,120 --> 02:21:28,080 >>THANK YOU. 2599 02:21:28,080 --> 02:21:38,480 >>THANK YOU VERY MUCH. 2600 02:21:54,080 --> 02:21:56,280 >>NEURONS AND OTHERS SO DID YOU 2601 02:21:56,280 --> 02:21:59,440 THINK OF LOOKING INTO OTHER 2602 02:21:59,440 --> 02:22:05,560 NERVES, FOR EXAMPLE, THE -- THE 2603 02:22:05,560 --> 02:22:08,200 CARROTTED THAT MAY GIVE A 2604 02:22:08,200 --> 02:22:10,120 STRONGER SIGNALS IN RESPONSE TO 2605 02:22:10,120 --> 02:22:10,360 HYPOXIA. 2606 02:22:10,360 --> 02:22:10,920 >>CERTAINLY. 2607 02:22:10,920 --> 02:22:13,760 WE'RE NOT FOCUS ON HYPOXY EXCEPT 2608 02:22:13,760 --> 02:22:15,920 A CHALLENGE TO MAKE SURE WE HAVE 2609 02:22:15,920 --> 02:22:18,240 INPUTS UP TO THE BRAIN STEM THAT 2610 02:22:18,240 --> 02:22:18,880 EFFECT BREATHING CONTROL SO 2611 02:22:18,880 --> 02:22:23,440 WE'RE FOCUSED ON INSENATORS FORR 2612 02:22:23,440 --> 02:22:23,680 THE LUNG. 2613 02:22:23,680 --> 02:22:25,360 WE HOPE TO DO THAT WORK AS WELL 2614 02:22:25,360 --> 02:22:26,600 OF COURSE AND TALK ABOUT MORE OF 2615 02:22:26,600 --> 02:22:27,920 THE REST OF THE CONTROL CIRCUIT 2616 02:22:27,920 --> 02:22:30,680 TREE WITHIN THE BRAIN STEM. 2617 02:22:30,680 --> 02:22:31,400 GREAT POINT. 2618 02:22:31,400 --> 02:22:33,320 WE'D LIKE TO DO IT AND WE'LL 2619 02:22:33,320 --> 02:22:33,680 KEEP WORKING. 2620 02:22:33,680 --> 02:22:36,920 >>THANK YOU. 2621 02:22:36,920 --> 02:22:38,160 >>THANK YOU VERY MUCH AND NOW 2622 02:22:38,160 --> 02:22:48,640 WE'LL MOVE TO THE NEXT TALK. 2623 02:22:51,440 --> 02:22:52,800 GOOD AFTERNOON, EVERYONE. 2624 02:22:52,800 --> 02:22:55,440 MY NAME IS PENG LI AND I'M FROM 2625 02:22:55,440 --> 02:23:00,280 THE UNIVERSITY O MICHIGAN, GO 2626 02:23:00,280 --> 02:23:00,520 BLUE. 2627 02:23:00,520 --> 02:23:02,160 I'D LIKE TO THANK THE BLUE PRINT 2628 02:23:02,160 --> 02:23:03,560 FOR FUNDING OUR PROJECT AND 2629 02:23:03,560 --> 02:23:05,320 THANK YOU TO THE ORGANIZERS FOR 2630 02:23:05,320 --> 02:23:11,360 HAVING ME HERE TO SHARE OUR 2631 02:23:11,360 --> 02:23:11,640 WORK. 2632 02:23:11,640 --> 02:23:13,680 OUR LAB IS INTERESTING SHOWING 2633 02:23:13,680 --> 02:23:16,320 HOW OUR BRAIN INTEGRATE SENSORY 2634 02:23:16,320 --> 02:23:17,760 STIM YOU LIGHT AND CONTROLLING 2635 02:23:17,760 --> 02:23:24,200 BEHAVIOR SO WITH THE FOCUS ON 2636 02:23:24,200 --> 02:23:27,240 BREATHING. 2637 02:23:27,240 --> 02:23:36,160 BECAUSE BREATHING -- SO, BECAUSE 2638 02:23:36,160 --> 02:23:38,640 BREATHING IS A VITAL BODY 2639 02:23:38,640 --> 02:23:43,960 FUNCTION IN HOMEOSTASIS AND IT'S 2640 02:23:43,960 --> 02:23:50,600 EFFECTED AND WITH CONSEQUENCES. 2641 02:23:50,600 --> 02:23:51,800 BREATHING A CRITICAL PROCESS IN 2642 02:23:51,800 --> 02:23:54,120 LINKING OR MEDIATING THE 2643 02:23:54,120 --> 02:23:55,120 INTERACTION BETWEEN THE BRAIN 2644 02:23:55,120 --> 02:24:00,200 ANDED BOW OAND BODY AND THE ONLC 2645 02:24:00,200 --> 02:24:00,800 BODY FUNCTION THAT CAN BE 2646 02:24:00,800 --> 02:24:02,080 CONTROLLED BOTH OF VOLUNTARILY 2647 02:24:02,080 --> 02:24:04,640 AND THE INVOLUNTARILY. 2648 02:24:04,640 --> 02:24:09,880 AND IT'S A BEHAVIOR BREATHING IS 2649 02:24:09,880 --> 02:24:11,760 ALSO APP TRACTABLE AND WE CAN 2650 02:24:11,760 --> 02:24:13,200 SIMPLY TRACE DIFFERENT 2651 02:24:13,200 --> 02:24:15,360 PARAMETERS TO A MATTER OF 2652 02:24:15,360 --> 02:24:16,280 BREATHING WHAT IS SHOWING HERE 2653 02:24:16,280 --> 02:24:19,560 IS A BREATHING FROM THE RESTING 2654 02:24:19,560 --> 02:24:20,520 STATE BECAUSE YOU HAVE A 2655 02:24:20,520 --> 02:24:24,000 BREATHING PATTERN OR A REGULAR 2656 02:24:24,000 --> 02:24:25,600 BREATH AND IN ADDITION TO THESE 2657 02:24:25,600 --> 02:24:26,960 REGULAR BREATHING PATTERNS, WE 2658 02:24:26,960 --> 02:24:28,760 ALSO HAVE OTHER BREATHING 2659 02:24:28,760 --> 02:24:39,280 PATTERNS WHICH HAVE SIMULATED 2660 02:24:55,000 --> 02:24:57,200 WE STARTED BY DESECTING THE 2661 02:24:57,200 --> 02:25:00,600 NEURONS SO FIRST WE CARRY OUT A 2662 02:25:00,600 --> 02:25:04,240 SINGLE CELL OF THE NTS REGION OF 2663 02:25:04,240 --> 02:25:08,280 THE FROM THERE WE IDENTIFY THE 2664 02:25:08,280 --> 02:25:11,280 DIFFERENT CELL TYPES AND 2665 02:25:11,280 --> 02:25:12,960 INCLUDING NEURONS AND OTHER CELL 2666 02:25:12,960 --> 02:25:23,200 TYPES IN THIS. 2667 02:25:35,200 --> 02:25:40,200 >>WE ACTIVATED THE CELLS AND AS 2668 02:25:40,200 --> 02:25:42,600 SUBSET AND SO BECAUSE NTS IS 2669 02:25:42,600 --> 02:25:44,800 ESSENTIAL INTO MEDIATING 2670 02:25:44,800 --> 02:25:46,120 BREATHING IT'S NOT SURPRISING 2671 02:25:46,120 --> 02:25:47,840 THAT WE SAW BREATHING IS 2672 02:25:47,840 --> 02:25:49,880 EFFECTING WHEN WE ACTIVATED 2673 02:25:49,880 --> 02:25:51,120 DIFFERENT SUBSETS SO WHEN WE 2674 02:25:51,120 --> 02:25:53,000 ACTIVATED THE ACCESS OF THE 2675 02:25:53,000 --> 02:25:55,640 NEURONS WE OFTEN SEE A 2676 02:25:55,640 --> 02:25:58,880 INSPIRATION INDUCED AND WHEN WE 2677 02:25:58,880 --> 02:26:00,000 ACTIVATE THE INWILL TO BE 2678 02:26:00,000 --> 02:26:04,120 NEURONS WE SAW THE BREATHING AND 2679 02:26:04,120 --> 02:26:07,760 LEN WE ZOOM INTO THE SUBSET OF 2680 02:26:07,760 --> 02:26:09,840 THE NEURONS AND FOR EXAMPLE HERE 2681 02:26:09,840 --> 02:26:12,880 WHEN WE ACTIVATE A SMALL SUBSET 2682 02:26:12,880 --> 02:26:16,400 OF THE NEURONS SPECIFICALLY 2683 02:26:16,400 --> 02:26:17,760 EXPRESSING RELEASING PEP TIGHTS 2684 02:26:17,760 --> 02:26:20,840 REPRESENTING THE TWO AND THROW 2685 02:26:20,840 --> 02:26:23,720 AND WE SAW A SIGH IS INDUCED SO 2686 02:26:23,720 --> 02:26:25,720 WHAT IS A SIGH? 2687 02:26:25,720 --> 02:26:28,600 THE WE OFTEN TALKED ABOUT IT 2688 02:26:28,600 --> 02:26:33,120 LONG LARGE DEEP BREATHE SEWATED 2689 02:26:33,120 --> 02:26:34,800 TO EMOTION AND STRESS, RELIEF 2690 02:26:34,800 --> 02:26:37,360 AND SADNESS. 2691 02:26:37,360 --> 02:26:39,640 BUT AS CAN YOU SEE HERE IT'S A 2692 02:26:39,640 --> 02:26:41,320 INSPIRATION FOLLOWED BY A 2693 02:26:41,320 --> 02:26:42,720 ELONGATED EXPIRATION AND IT 2694 02:26:42,720 --> 02:26:44,760 TURNS OUT THAT WE SAW 2695 02:26:44,760 --> 02:26:46,800 SPONTANEOUSLY AND WE CALL THIS A 2696 02:26:46,800 --> 02:26:50,960 BASAL SIZE AND HUMAN SIZE FIVE 2697 02:26:50,960 --> 02:26:52,160 TO 10 MINUTES AND EVERY TWO 2698 02:26:52,160 --> 02:26:53,640 MINUTES SO YOU PAY ATTENTION TO 2699 02:26:53,640 --> 02:26:55,520 YOUR OWN BREATHING, YOU WILL 2700 02:26:55,520 --> 02:26:57,320 NOTICE ONE TO TWO SIZE IN THE 2701 02:26:57,320 --> 02:27:01,000 REST OF IT AND THIS SIZE ARE 2702 02:27:01,000 --> 02:27:02,760 ESSENTIAL INFORM THE COM APPS 2703 02:27:02,760 --> 02:27:04,480 AND THE DOCTORS PROGRAM THESE 2704 02:27:04,480 --> 02:27:07,480 SIDES INTO THE VENTILATOR TO 2705 02:27:07,480 --> 02:27:10,120 MAINTAIN THE TELL MINUTE TARRY 2706 02:27:10,120 --> 02:27:11,320 FUNCTIONS OF THE PATIENTS AND IT 2707 02:27:11,320 --> 02:27:14,560 CANNING REGULATED BY DIFFERENT 2708 02:27:14,560 --> 02:27:17,440 STIMULI AND SUCH AS HYPOXIA 2709 02:27:17,440 --> 02:27:20,320 WHICH SO I STRONG STIMULUS IN 2710 02:27:20,320 --> 02:27:20,960 ENTHUSING SIZE. 2711 02:27:20,960 --> 02:27:22,480 THERE ARE OTHER CONDITIONS WITH 2712 02:27:22,480 --> 02:27:26,360 ELEVATED SIZE AND INCLUDING 2713 02:27:26,360 --> 02:27:29,560 CHRONIC DISORDERS AND THE PANIC 2714 02:27:29,560 --> 02:27:31,240 DISORDERS AND WE CAN ALSO 2715 02:27:31,240 --> 02:27:32,360 VOLUNTARY SIGH BECAUSE IT'S HOW 2716 02:27:32,360 --> 02:27:35,720 WE CAN VOLUNTARILY CONTROL OUR 2717 02:27:35,720 --> 02:27:37,240 OTHER BREATHING PATTERNS. 2718 02:27:37,240 --> 02:27:39,560 SO, HOW IS A SIDE CONTROL. 2719 02:27:39,560 --> 02:27:43,080 A COUPLE YEARS AGO WE IDENTIFIED 2720 02:27:43,080 --> 02:27:45,960 SMALL SUBSET OF NEURONS IN THE 2721 02:27:45,960 --> 02:27:47,840 ONE SIDE OF THE BRAIN STREAM AND 2722 02:27:47,840 --> 02:27:51,040 CONNECTING TWO KEY BREATHING 2723 02:27:51,040 --> 02:28:01,360 CONTROL CENTERS AND 2724 02:28:14,240 --> 02:28:18,640 >>FOR THE RHYTHM GENERATION. 2725 02:28:18,640 --> 02:28:19,920 THIS NEURONS ONLY THE SIGH IS 2726 02:28:19,920 --> 02:28:23,240 EFFECTED AND NOW THE BREATHING 2727 02:28:23,240 --> 02:28:26,000 AND SO SUGGEST THEY PLAY A 2728 02:28:26,000 --> 02:28:27,760 DEDICATED CONTROL IN CONTROLLING 2729 02:28:27,760 --> 02:28:29,280 THESE BREATHING PATTERNS AND WE 2730 02:28:29,280 --> 02:28:31,400 FOLLOW THIS UP LOOKING INTO THE 2731 02:28:31,400 --> 02:28:33,560 EMOTIONAL SIDE AND WE FOUND THE 2732 02:28:33,560 --> 02:28:36,720 STRESS WE ALSO CALL IT CLASS 2733 02:28:36,720 --> 02:28:46,480 CLAUSE TRACLAUSTROPHOBIA AND FRE 2734 02:28:46,480 --> 02:28:48,600 NEURONS WE IDENTIFY THE DOZEN 2735 02:28:48,600 --> 02:28:59,160 REGIONS INCLUDING -- WE CAN INDE 2736 02:29:00,680 --> 02:29:03,080 STRESS RELATED BEHAVIOR SIMILAR 2737 02:29:03,080 --> 02:29:05,440 TO THE RESPONSE ELEVATED AND 2738 02:29:05,440 --> 02:29:15,960 WHEN WE SILENCE THIS PATHWAY, 2739 02:30:01,800 --> 02:30:05,520 >>IT'S SUFFICIENT IN INDUCING 2740 02:30:05,520 --> 02:30:07,840 WE NEXT WONDER IF THERE'S A 2741 02:30:07,840 --> 02:30:10,920 CIRCUIT OF FEEDING INTO THIS 2742 02:30:10,920 --> 02:30:14,240 NEURON IN REGULATING THE 2743 02:30:14,240 --> 02:30:15,200 HYPOTHESIS AREA RESPONSE AS 2744 02:30:15,200 --> 02:30:18,720 PEOPLE MENTIONED EARLIER, IT'S A 2745 02:30:18,720 --> 02:30:24,880 MAJOR OX DEPART OXY DENT SO WE E 2746 02:30:24,880 --> 02:30:27,240 NEURONS AND USE A RETRO TRADE 2747 02:30:27,240 --> 02:30:28,880 TRACING IN COMBINATION THERE'S 2748 02:30:28,880 --> 02:30:30,800 TRACING FROM THE BODY AND IN 2749 02:30:30,800 --> 02:30:33,000 DEED, WE FOUND A CO LOCALIZATION 2750 02:30:33,000 --> 02:30:43,680 OF THIS IN THE VAGUS NIH SO VAG. 2751 02:30:44,480 --> 02:30:47,680 AND THE NEXT WE USE A GENETICS 2752 02:30:47,680 --> 02:30:51,000 TO SILENCING THE GPR NEURONS AND 2753 02:30:51,000 --> 02:30:54,560 IN DEED, THE HYPOXY INDUCES IS A 2754 02:30:54,560 --> 02:30:57,280 SPECIFICALLY REDUCED AND I'M NOT 2755 02:30:57,280 --> 02:31:02,200 SHOWING YOU HERE IS THE BASAL 2756 02:31:02,200 --> 02:31:04,400 SIDE OR OTHER RESPONSE WAS NOT 2757 02:31:04,400 --> 02:31:04,960 EFFECTED. 2758 02:31:04,960 --> 02:31:07,120 SO SUGGESTING THESE NEURONS HAVE 2759 02:31:07,120 --> 02:31:12,160 A SPECIFIC CONTROL IN MEDIATING 2760 02:31:12,160 --> 02:31:13,640 HIGH TOXIA SO WE LOOK AT NEURONS 2761 02:31:13,640 --> 02:31:15,680 AND LET'S LOOK AT ANOTHER 2762 02:31:15,680 --> 02:31:18,560 POPULATION WHICH IS A NEURONS IN 2763 02:31:18,560 --> 02:31:23,520 THE NTS SO WHEN WE ACTIVATED 2764 02:31:23,520 --> 02:31:29,240 THESE CLASS NEURONS, WE SAW A 2765 02:31:29,240 --> 02:31:33,160 STEREO TYPE BRACKET BREATHING SS 2766 02:31:33,160 --> 02:31:34,480 THIS BREATHING PATTERNS. 2767 02:31:34,480 --> 02:31:36,360 SO WE LOOKED INTO LITERATURE 2768 02:31:36,360 --> 02:31:39,720 FROM HUMAN AND OTHER SPECIES AND 2769 02:31:39,720 --> 02:31:41,880 IT LOOKS SIMILAR TO A COUGH. 2770 02:31:41,880 --> 02:31:49,520 SO WHAT IS A COUGH? 2771 02:31:49,520 --> 02:31:50,480 A COUGH IS A PROTECTIVE 2772 02:31:50,480 --> 02:31:53,960 BREATHING RESPONSE TO THE USE OF 2773 02:31:53,960 --> 02:31:54,320 YOUR AIRWAYS. 2774 02:31:54,320 --> 02:31:56,920 IT'S TRIGGERED BY THESE COUGH 2775 02:31:56,920 --> 02:31:59,000 INDUCING STIMULUS. 2776 02:31:59,000 --> 02:32:05,080 AND IT STARTED BY A COMPRESSION 2777 02:32:05,080 --> 02:32:08,160 PHASE WHICH IS A CLOSE AIR 2778 02:32:08,160 --> 02:32:10,720 PRESSURE BUILDUP IN OUR AIRWAYS 2779 02:32:10,720 --> 02:32:14,120 AND BECAUSE OF THE SUDDEN 2780 02:32:14,120 --> 02:32:15,280 OPENING OF THE AREA IT RUSHES 2781 02:32:15,280 --> 02:32:17,560 OUT FROM OUR AIRWAY WHICH IS 2782 02:32:17,560 --> 02:32:21,440 COUPLED WITH BODY MOVEMENT. 2783 02:32:21,440 --> 02:32:22,640 HOWEVER, WHETHER MOUTH COUGHS 2784 02:32:22,640 --> 02:32:24,720 HAVE BEEN DEBATED IN THE FIELD, 2785 02:32:24,720 --> 02:32:26,080 BECAUSE THEY'RE TINY AND IT'S 2786 02:32:26,080 --> 02:32:29,720 HARD TO DETECT THE BREATHING 2787 02:32:29,720 --> 02:32:30,000 PATTERN. 2788 02:32:30,000 --> 02:32:33,120 WE DECIDED TO CHECK OURSELVES. 2789 02:32:33,120 --> 02:32:36,080 SO WE NUMBER YOU LIESED THE 2790 02:32:36,080 --> 02:32:38,560 EXACT INTEREST WHICH IS KNOWN AS 2791 02:32:38,560 --> 02:32:43,720 A PASSIVE AGENT IN PATIENTS SO 2792 02:32:43,720 --> 02:32:46,440 DOCTORS USED THESE IN PATIENTS. 2793 02:32:46,440 --> 02:32:54,680 SO WE APPLIED THESE CHALLENGE TO 2794 02:32:54,680 --> 02:32:56,680 THE ANIMALS AND WE INDUCES IT 2795 02:32:56,680 --> 02:32:58,120 WITH INSPIRATION, COM OPERATION 2796 02:32:58,120 --> 02:33:00,680 PHASE AND EXPLOSIVES PHASE AND 2797 02:33:00,680 --> 02:33:02,720 IT'S A COUPLED WITH THE SUM AND 2798 02:33:02,720 --> 02:33:06,280 THE OTHER PHYSIOLOGICAL 2799 02:33:06,280 --> 02:33:10,160 MATTERMENTS SO THEN, WE PULL THE 2800 02:33:10,160 --> 02:33:14,400 ANIMAL, THE ANIMALS INTO THIS 2801 02:33:14,400 --> 02:33:20,000 PARADIGM AND IN DEED WE SAW THE 2802 02:33:20,000 --> 02:33:23,240 IDENTICAL PATTERN WAS INDUCED. 2803 02:33:23,240 --> 02:33:25,160 AND THEN WE SILENCEDDED THESE 2804 02:33:25,160 --> 02:33:28,120 NEURONS AND WE FOUND COUGH IS 2805 02:33:28,120 --> 02:33:31,160 DRAMATICALLY REDUCED SO THESE 2806 02:33:31,160 --> 02:33:33,680 SUGGEST THAT THESE NEURONS IS 2807 02:33:33,680 --> 02:33:36,120 BOTH NECESSARY AND SUFFICIENT 2808 02:33:36,120 --> 02:33:36,440 FOR COUGH. 2809 02:33:36,440 --> 02:33:41,680 AND IN THE MEANTIME, WE ALSO 2810 02:33:41,680 --> 02:33:44,280 OBSERVE THE OTHER BREATHING 2811 02:33:44,280 --> 02:33:45,360 POTTENS AND RESPONSE AND NOW 2812 02:33:45,360 --> 02:33:50,480 THOSE WERE EFFECTED, BUT THESE 2813 02:33:50,480 --> 02:33:52,320 MANIPULATION. 2814 02:33:52,320 --> 02:33:53,800 NEXT WE TRACE THE UPSTREAM AND 2815 02:33:53,800 --> 02:33:55,440 DOWNSTREAM OF THESE NEURONS AND 2816 02:33:55,440 --> 02:33:58,040 WE FOUND THAT THEY RECEIVED THE 2817 02:33:58,040 --> 02:34:02,720 MEET EIGHTING THE PASSIVE 2818 02:34:02,720 --> 02:34:05,080 STIMULUS AND THEY PROJECT TO 2819 02:34:05,080 --> 02:34:07,480 DIFFERENT DOWNSTREAM REGIONS IN 2820 02:34:07,480 --> 02:34:09,120 THE BRAIN STEM IN CONTROLLING 2821 02:34:09,120 --> 02:34:11,400 THE COMPLIMENTARY AND THE 2822 02:34:11,400 --> 02:34:14,320 SEQUENTIAL MOTOR OUT MODES OF A 2823 02:34:14,320 --> 02:34:14,680 TOUGH. 2824 02:34:14,680 --> 02:34:19,160 SO WE HAVE HIGH POTH A SIS THESE 2825 02:34:19,160 --> 02:34:21,240 NEURONS AS PART OF THE IMPORTANT 2826 02:34:21,240 --> 02:34:27,080 PART OF THE TOUGH CENTRAL AND 2827 02:34:27,080 --> 02:34:31,360 GENERATOR AND SO IN SUMMARY, WE 2828 02:34:31,360 --> 02:34:33,240 STARTED MOLECULAR AND FUNCTIONAL 2829 02:34:33,240 --> 02:34:36,560 ANALYSIS OF NTS NEURONS AND 2830 02:34:36,560 --> 02:34:38,840 IDENTIFIED TWO SMALL SUBSETS OF 2831 02:34:38,840 --> 02:34:42,320 NEURONS THAT GRP NEURONS AND THE 2832 02:34:42,320 --> 02:34:44,920 THEY ARE REGULATING TWO DISTINCT 2833 02:34:44,920 --> 02:34:47,360 BREATHING PATTERNS AS A SIGH AND 2834 02:34:47,360 --> 02:34:47,800 A COUGH. 2835 02:34:47,800 --> 02:34:53,560 WHICH ARE ALSO IMPORTANT IN THE 2836 02:34:53,560 --> 02:34:54,640 PATHOLOGICAL CONDITIONS. 2837 02:34:54,640 --> 02:34:56,520 WE FOUND THAT THEY'RE MEDIATING 2838 02:34:56,520 --> 02:35:00,600 HYPOXY INDUCED SIGH AND CHARGING 2839 02:35:00,600 --> 02:35:01,600 INDUCING THE COUGH RESPECTIVELY 2840 02:35:01,600 --> 02:35:07,840 AND BY TRACING TH CIRCUIT, WE 2841 02:35:07,840 --> 02:35:10,240 IDENTIFIED MEDIATING THESE TWO 2842 02:35:10,240 --> 02:35:12,960 BEHAVIORS AND WE ALSO PROPOSE TO 2843 02:35:12,960 --> 02:35:15,440 CHECK AND TO TRACE THEIR DOWN 2844 02:35:15,440 --> 02:35:16,640 STREAMS THROUGH OUT THE BRAIN TO 2845 02:35:16,640 --> 02:35:19,440 FIGURE OUT THE BRAIN MAP 2846 02:35:19,440 --> 02:35:23,200 REPRESENTING THESE INTRO 2847 02:35:23,200 --> 02:35:23,600 ACCEPTIVE STATES. 2848 02:35:23,600 --> 02:35:31,000 WITH THAT, I'D LIKE TO THANK MY 2849 02:35:31,000 --> 02:35:31,320 LAB. 2850 02:35:31,320 --> 02:35:33,000 AND OUR COLLABORATORS AND THE 2851 02:35:33,000 --> 02:35:34,600 FUNDING AGENTS. 2852 02:35:34,600 --> 02:35:43,200 ESPECIALLY THE BLUE PRINT NEURO 2853 02:35:43,200 --> 02:35:43,800 INTERCEPTION ON INTEROCEPTION 2854 02:35:43,800 --> 02:35:45,360 AND THE WORK THAT I PRESENTED 2855 02:35:45,360 --> 02:35:45,560 TODAY. 2856 02:35:45,560 --> 02:35:46,400 THANK YOU. 2857 02:35:46,400 --> 02:35:49,800 [APPLAUSE] 2858 02:35:49,800 --> 02:35:52,200 >>THANK YOU, VERY MUCH. 2859 02:35:52,200 --> 02:35:54,960 WE HAVE ONE QUESTION. 2860 02:35:54,960 --> 02:35:55,880 >>NICE WORK. 2861 02:35:55,880 --> 02:36:01,160 I WANTED TO YOU ASK IF YOU SAW 2862 02:36:01,160 --> 02:36:07,560 PHRG NEURO GROUPS. 2863 02:36:07,560 --> 02:36:11,080 THEY PROJECT AND THE GRPR 2864 02:36:11,080 --> 02:36:13,240 NEURONS AND FOR THE NEURONS 2865 02:36:13,240 --> 02:36:16,200 PROJECTED TO THE REGION AND ALSO 2866 02:36:16,200 --> 02:36:20,440 THE RFRG TO REGULATE DIFFERENT 2867 02:36:20,440 --> 02:36:22,280 ASPECTS OF THE COST. 2868 02:36:22,280 --> 02:36:22,640 >>THANK YOU. 2869 02:36:22,640 --> 02:36:23,600 >>YEAH. 2870 02:36:23,600 --> 02:36:25,640 >>JUST ONE OTHER QUICK 2871 02:36:25,640 --> 02:36:26,040 QUESTION. 2872 02:36:26,040 --> 02:36:27,280 SO YOU MENTIONED THAT BREATHING 2873 02:36:27,280 --> 02:36:28,560 IS UNDER VOLUNTARY CONTROL AND 2874 02:36:28,560 --> 02:36:30,840 I'M WONDERING WHEN YOU THINK 2875 02:36:30,840 --> 02:36:33,600 THAT ONE COULD TRAIN A MOUSE TO 2876 02:36:33,600 --> 02:36:33,800 COUGH? 2877 02:36:33,800 --> 02:36:35,880 >>THAT'S A GOOD QUESTION MANY 2878 02:36:35,880 --> 02:36:37,560 OF IT'S ON OUR WISH LIST. 2879 02:36:37,560 --> 02:36:39,520 WE HOPE WE CAN TRAIN AN ANIMAL. 2880 02:36:39,520 --> 02:36:40,800 IF YOU HAVE ANY SUGGESTIONS, LET 2881 02:36:40,800 --> 02:36:41,320 US KNOW. 2882 02:36:41,320 --> 02:36:41,720 [LAUGHTER] 2883 02:36:41,720 --> 02:36:42,040 >>THANK YOU. 2884 02:36:42,040 --> 02:36:49,280 >>WE'LL MOVE ON TO THE NEXT 2885 02:36:49,280 --> 02:36:49,480 SPEAKER. 2886 02:36:49,480 --> 02:36:51,080 >>GOOD AFTERNOON. 2887 02:36:51,080 --> 02:36:52,920 I WOULD LIKE TO START BY 2888 02:36:52,920 --> 02:36:55,880 THANKING THE MEETING ORGANIZING 2889 02:36:55,880 --> 02:36:58,560 COMMITTEE AND Dr. CHEN, AND 2890 02:36:58,560 --> 02:37:00,040 MANY OTHERS FOR THE KIND 2891 02:37:00,040 --> 02:37:01,120 INVITATION TO BE HERE TODAY. 2892 02:37:01,120 --> 02:37:03,480 MY LAB GROUP IS INTERESTED IN 2893 02:37:03,480 --> 02:37:04,760 UNDERSTANDING THE DESCENDING OR 2894 02:37:04,760 --> 02:37:09,000 THE EFFECTER LYMPH INTEROCEPTION 2895 02:37:09,000 --> 02:37:10,400 CIRCUITS THAT REGULATE THE 2896 02:37:10,400 --> 02:37:10,920 HEART. 2897 02:37:10,920 --> 02:37:12,520 HERE ARE MY DISCLOSURES AND 2898 02:37:12,520 --> 02:37:14,120 FUNDING SOURCES. 2899 02:37:14,120 --> 02:37:17,840 AS WELL AS AN ACKNOWLEDGMENT OF 2900 02:37:17,840 --> 02:37:20,200 MY COLLEAGUES IN UCLA AND I'M IN 2901 02:37:20,200 --> 02:37:21,840 A LARGE GROUP OF PHYSICIAN 2902 02:37:21,840 --> 02:37:22,840 SCIENTISTS INTERESTED IN WHAT 2903 02:37:22,840 --> 02:37:24,840 WE'RE TALKING ABOUT TODAY. 2904 02:37:24,840 --> 02:37:28,360 SO, MY GROUP IS PARTICULARLY 2905 02:37:28,360 --> 02:37:30,520 INTERESTED IN THIS -- THIS VIDEO 2906 02:37:30,520 --> 02:37:32,720 IS NOT GOING TO PLAY. 2907 02:37:32,720 --> 02:37:35,520 WE'RE INTERESTED IN ARRHYTHMIA 2908 02:37:35,520 --> 02:37:37,680 IS THE LEADING CAUSE OF DEATH IN 2909 02:37:37,680 --> 02:37:39,200 DEVELOPED NATIONS AND OUR LAB 2910 02:37:39,200 --> 02:37:41,120 GROUP IS PARTICULARLY INTERESTED 2911 02:37:41,120 --> 02:37:43,600 IN THE DEFENDING CONTROLS SO 2912 02:37:43,600 --> 02:37:46,880 WITHIN THE SYMPATHETIC NERVOUS 2913 02:37:46,880 --> 02:37:47,840 SYSTEM THAT REGULATES CARDIAC 2914 02:37:47,840 --> 02:37:50,360 FUNCTION AND WE USE MODELS, 2915 02:37:50,360 --> 02:37:52,480 MICE, PIGS AND EVEN HUMANS, YES, 2916 02:37:52,480 --> 02:37:55,000 HUMANS ARE MODEL ORGANISM IN OUR 2917 02:37:55,000 --> 02:37:58,200 LAB GROUP AND WE USE 2918 02:37:58,200 --> 02:38:00,200 MULTI-STALE, MULTI MODAL 2919 02:38:00,200 --> 02:38:02,480 APPROACHES FOR SYMPATHETIC SAM 2920 02:38:02,480 --> 02:38:07,360 BOLLING IN CARDIAC PATHOLOGY AND 2921 02:38:07,360 --> 02:38:07,800 ARRHYTHMIA. 2922 02:38:07,800 --> 02:38:08,920 HEART DISEASE IS THE LEADING 2923 02:38:08,920 --> 02:38:12,480 CAUSE OF DEATH AND 34 PEOPLE DIE 2924 02:38:12,480 --> 02:38:15,320 EVERY MINUTE OF SUDDEN CARDIAC 2925 02:38:15,320 --> 02:38:17,200 DEATH AND THIS RESEARCH AREAS IS 2926 02:38:17,200 --> 02:38:18,560 PARTICULARLY IMPORTANT BECAUSE 2927 02:38:18,560 --> 02:38:20,200 OF ALL THE PATIENTS AT RISK FOR 2928 02:38:20,200 --> 02:38:22,240 SUDDEN DEATH, IF YOU LOOK AT 2929 02:38:22,240 --> 02:38:24,760 THIS BLUE OVAL HERE AND PATIENTS 2930 02:38:24,760 --> 02:38:26,600 WHO HAVE SUDDEN DEATH WERE ONLY 2931 02:38:26,600 --> 02:38:28,960 ABLE TO RECOGNIZE A VERY, VERY 2932 02:38:28,960 --> 02:38:30,600 PREPORTION OF THEM AT RISK FOR 2933 02:38:30,600 --> 02:38:32,480 SUDDEN DEATH SO, RESEARCH INTO 2934 02:38:32,480 --> 02:38:35,760 THIS AREA IS CRITICALLY NEEDED. 2935 02:38:35,760 --> 02:38:37,080 WE GOT INTERESTED IN THIS AREA 2936 02:38:37,080 --> 02:38:39,480 BECAUSE OF A THERAPY THAT WE 2937 02:38:39,480 --> 02:38:41,320 FOUND OUT OF DESPERATION WHICH 2938 02:38:41,320 --> 02:38:44,040 IS OUR PATIENTS WITH SEVERE 2939 02:38:44,040 --> 02:38:48,160 ARRHYTHMIA WERE OFFERED THERAPY 2940 02:38:48,160 --> 02:38:50,560 CARDIAC REMOVAL OF THE PART THE 2941 02:38:50,560 --> 02:38:52,200 GANGLION AND THE SECOND AND 2942 02:38:52,200 --> 02:38:53,600 THIRD AND FOURTH AUTHORIZE AS 2943 02:38:53,600 --> 02:38:55,160 TICK BODIES OF THE SYMPATHETIC 2944 02:38:55,160 --> 02:38:57,040 CHAIN WHICH REPRESENTS THE POST 2945 02:38:57,040 --> 02:38:58,640 GANGLION I CAN SYMPATHETIC 2946 02:38:58,640 --> 02:39:08,000 CONTROL OF THE HEART. 2947 02:39:08,000 --> 02:39:09,280 IT SAVED LIVES AND PATIENTS WENT 2948 02:39:09,280 --> 02:39:10,440 ON TO DO WELL. 2949 02:39:10,440 --> 02:39:12,080 THIS TURNED OUR ATTENTION TO 2950 02:39:12,080 --> 02:39:12,920 CARDIAC NEURAL CONTROL. 2951 02:39:12,920 --> 02:39:14,480 MOST OF YOU NEED NO INTRODUCTION 2952 02:39:14,480 --> 02:39:17,360 TO THE FACT THAT THE HEART IS 2953 02:39:17,360 --> 02:39:19,080 DENSELY INNERVATED AND THIS IS 2954 02:39:19,080 --> 02:39:21,120 PLAYING SO I'LL START IT AGAIN. 2955 02:39:21,120 --> 02:39:23,000 IT'S A IMAGE OF A MOUSE HEART 2956 02:39:23,000 --> 02:39:25,680 JUST SHOWING HOW DENSELY 2957 02:39:25,680 --> 02:39:26,640 INNERVATED THE HEART IS. 2958 02:39:26,640 --> 02:39:28,560 IN ADDITION TO THAT, THERE ARE 2959 02:39:28,560 --> 02:39:30,160 NEURONS THAT SIT WITHIN EPI CARD 2960 02:39:30,160 --> 02:39:33,320 Y'ALL GANGLIA AND TOGETHER 2961 02:39:33,320 --> 02:39:40,080 REGULATE THE HEART AS SHOWN 2962 02:39:40,080 --> 02:39:42,280 HERE. 2963 02:39:42,280 --> 02:39:47,960 THATESSENTIALLY WE LOOK AT THE T 2964 02:39:47,960 --> 02:39:50,760 OF A SERIES OF FEEDBACK LOOPS 2965 02:39:50,760 --> 02:39:51,920 WHERE INFORMATION FROM THE HEART 2966 02:39:51,920 --> 02:39:54,040 IS PROCESSED BY NEURONS WITHIN 2967 02:39:54,040 --> 02:39:57,200 THE EPI CARDIAL GANGLIA AND 2968 02:39:57,200 --> 02:39:59,400 INFORMATION IS TAKEN UP TO THE 2969 02:39:59,400 --> 02:40:03,840 WE'RE TAKING OUT OF PATIENTS AND 2970 02:40:03,840 --> 02:40:06,920 THROUGH THE DRG SPINAL CORD AND 2971 02:40:06,920 --> 02:40:09,960 BACK TO THE HEART AND TO BRAIN 2972 02:40:09,960 --> 02:40:11,080 STEM AND BACK TO THE HEART. 2973 02:40:11,080 --> 02:40:13,400 WE ARE FOCUSING DOWN TO THE 2974 02:40:13,400 --> 02:40:16,320 HEART AND THE REASON FOR THAT, 2975 02:40:16,320 --> 02:40:19,520 AGAIN, IS THE FACT THAT WE KNOW 2976 02:40:19,520 --> 02:40:22,600 THAT IT IS A CAUSE OR A DRIVER 2977 02:40:22,600 --> 02:40:24,160 OF ARRHYTHMIA IN PATIENTS. 2978 02:40:24,160 --> 02:40:25,760 IF YOU TAKE A PATIENT WITH A 2979 02:40:25,760 --> 02:40:27,080 HEART ATTACK WE'VE LEARNED OVER 2980 02:40:27,080 --> 02:40:30,480 THE YEARS THAT THERE ARE 2981 02:40:30,480 --> 02:40:32,000 MEDIATED ALTERATIONS THAT HAPPEN 2982 02:40:32,000 --> 02:40:33,560 TO NEURONS WITHIN THE GANGLION 2983 02:40:33,560 --> 02:40:35,440 AND AT THE LEVEL OF THE HEART 2984 02:40:35,440 --> 02:40:37,240 THAT TOGETHER TRIGGERED THOSE 2985 02:40:37,240 --> 02:40:38,960 DANGEROUS ARRHYTHMIAS THAT I 2986 02:40:38,960 --> 02:40:41,080 JUST SPOKEN ABOUT. 2987 02:40:41,080 --> 02:40:43,840 IN ADDITION TO THAT, WHEN THE 2988 02:40:43,840 --> 02:40:45,720 HEART IS CHRONICALLY INJURED, 2989 02:40:45,720 --> 02:40:50,320 THESE NEURONS UNDERGO A REALLY 2990 02:40:50,320 --> 02:40:53,520 LARGE AMOUNT OF ENCLOUD OX DAY 2991 02:40:53,520 --> 02:40:55,160 TIVE STRESS AND ACTIVATION OF 2992 02:40:55,160 --> 02:40:56,880 GLEE OWE CELLS AND ALTERATION IN 2993 02:40:56,880 --> 02:41:07,320 NEURO TRANSMITTER USE BUT 2994 02:41:09,880 --> 02:41:11,640 CONTROL OF THE HEART ARE MAVOR 2995 02:41:11,640 --> 02:41:14,880 OR DRIVERS THAT CAUSE PATIENTS 2996 02:41:14,880 --> 02:41:17,080 TO DIE OF MORTALITY AND 2997 02:41:17,080 --> 02:41:17,360 MORBIDITY. 2998 02:41:17,360 --> 02:41:19,560 WE ARE TACKLING FUNDAMENTAL 2999 02:41:19,560 --> 02:41:22,480 QUESTIONS THAT ARE ADDRESS TO 3000 02:41:22,480 --> 02:41:24,120 THE LIMB OF THE CIRC SECRETARY'S 3001 02:41:24,120 --> 02:41:26,120 ASPECTS OF THE CIRCUIT AS WELL 3002 02:41:26,120 --> 02:41:31,280 BUT WE'VE BEEN FOCUSING ON THE 3003 02:41:31,280 --> 02:41:33,880 SYMPATHETIC CARDIAC CIRCUIT AND 3004 02:41:33,880 --> 02:41:35,600 ASKING QUESTIONS SUCH AS, YOU 3005 02:41:35,600 --> 02:41:39,160 KNOW, WHAT ARE THE CARDIAC 3006 02:41:39,160 --> 02:41:40,360 SYMPATHETIC EFFECTOR NEURONS ARE 3007 02:41:40,360 --> 02:41:43,440 THEY DISTINCT FROM NEURONS THAT 3008 02:41:43,440 --> 02:41:45,240 HAVE OTHER TISSUES AND HOW MANY 3009 02:41:45,240 --> 02:41:46,760 SUCH SUB TYPES ARE THERE AND HOW 3010 02:41:46,760 --> 02:41:57,200 DO THEY CHANGE IN DISEASE? 3011 02:42:23,480 --> 02:42:26,440 >>SO TO ADDRESS THIS QUESTION 3012 02:42:26,440 --> 02:42:29,520 OF POSTDOC IN MY LAB AND IN 3013 02:42:29,520 --> 02:42:31,040 CONVERSATIONS WITH Dr. XI SUN 3014 02:42:31,040 --> 02:42:32,680 WHO SPOKE EARLIER ON THAT WE 3015 02:42:32,680 --> 02:42:34,920 SPOKE ON THE SIDELINES OF A NIH 3016 02:42:34,920 --> 02:42:36,720 MEETING AND THIS LED TO THIS 3017 02:42:36,720 --> 02:42:38,280 NICE PROJECT COMING OUT OF THE 3018 02:42:38,280 --> 02:42:40,520 LAB AND THE IDEA TO USE A 3019 02:42:40,520 --> 02:42:42,080 SIMILAR TRACING APPROACH TO 3020 02:42:42,080 --> 02:42:47,800 WHICH MOST OF YOU HAVE USED AND 3021 02:42:47,800 --> 02:42:50,560 IT'S TO INJECT IN THE HEART AND 3022 02:42:50,560 --> 02:42:51,160 HAVE IT TRACE BACK TO THE 3023 02:42:51,160 --> 02:42:55,040 GANGLION AND WHAT IS INTERESTING 3024 02:42:55,040 --> 02:43:02,880 IS THAT WE CAN IDENTIFY THE 3025 02:43:02,880 --> 02:43:04,760 TRANSCRIPT FOR THESE FLUORESCENT 3026 02:43:04,760 --> 02:43:06,440 PROTEINS TO IDENTIFY CARDIAC 3027 02:43:06,440 --> 02:43:07,520 NEURONS AND WE'VE DONE THE SAME 3028 02:43:07,520 --> 02:43:09,240 THINGS IN OTHER TISSUES AND SO 3029 02:43:09,240 --> 02:43:12,160 WE CAN TAKE THIS APPROACH TO 3030 02:43:12,160 --> 02:43:14,120 IDENTIFY CARDIAC SUB TYPES AND 3031 02:43:14,120 --> 02:43:15,520 PROFILE THEM USING SIMILAR 3032 02:43:15,520 --> 02:43:16,600 APPROACHES ASK TECHNIQUES THAT 3033 02:43:16,600 --> 02:43:18,160 YOU ARE ALL DOING. 3034 02:43:18,160 --> 02:43:19,920 HERE IS AN EXAMPLE OF OUR 3035 02:43:19,920 --> 02:43:21,240 TRACING, YOU SEE NICELY THAT WE 3036 02:43:21,240 --> 02:43:25,960 HOLE EYES TO THE CARN Y'ALL 3037 02:43:25,960 --> 02:43:28,400 MEDIAL SPOL AT THE CARDIO 3038 02:43:28,400 --> 02:43:29,680 PULMONARY POLE AND FROM OUR 3039 02:43:29,680 --> 02:43:33,840 SINGLE CELL RNA SEQUENCING DATA 3040 02:43:33,840 --> 02:43:36,120 WE IDENTIFY SEVEN SUB TYPES AND 3041 02:43:36,120 --> 02:43:39,720 THREE OF THEM WE SEE INNERVATE 3042 02:43:39,720 --> 02:43:40,520 THE HEART. 3043 02:43:40,520 --> 02:43:50,560 WE VALIDATED THE BECAUSE OF OUR 3044 02:43:50,560 --> 02:43:51,840 INTEREST IN TRANSLATING OUR 3045 02:43:51,840 --> 02:43:54,280 STUDIES TO HUMANS WE PROBE THESE 3046 02:43:54,280 --> 02:43:55,640 SAME CELL TYPES AND PIGS AND 3047 02:43:55,640 --> 02:43:57,560 HUMANS AND IDENTIFIED THEM FROM 3048 02:43:57,560 --> 02:44:01,640 THESE TWO MODELS AS WELL. 3049 02:44:01,640 --> 02:44:04,480 NOW LOOKING AT THE GENES ACROSS 3050 02:44:04,480 --> 02:44:05,920 THE SUBTYPES PARTICULARLY 3051 02:44:05,920 --> 02:44:07,960 FOCUSED ON THE ONES WE KNOW 3052 02:44:07,960 --> 02:44:12,480 INNERVATE THE HEART, ONE GENE 3053 02:44:12,480 --> 02:44:16,880 THAT JUMPED OUT WAS NEURO PEP 3054 02:44:16,880 --> 02:44:17,440 TYPE 1. 3055 02:44:17,440 --> 02:44:20,880 IT EXPRESSES A VERY HIGH LEVELS 3056 02:44:20,880 --> 02:44:24,200 OF NEURO PEPTIDE Y BUT SUBTYPE 3057 02:44:24,200 --> 02:44:28,320 NA1B IS MUCH LOWER LEVELS AND 3058 02:44:28,320 --> 02:44:31,400 AND THEY HAVE NO EXPRESSION OF 3059 02:44:31,400 --> 02:44:32,080 NEURO PEPTIDE Y AS WELL. 3060 02:44:32,080 --> 02:44:34,320 THE REASON IS JUMP OUTSIDE AT US 3061 02:44:34,320 --> 02:44:36,480 IS THERE'S A CONCEPT THAT 3062 02:44:36,480 --> 02:44:40,160 NEUROPEPTIDES OR NEURO 3063 02:44:40,160 --> 02:44:40,720 TRANSMITTER RE LEASE IN THE 3064 02:44:40,720 --> 02:44:44,560 HEART IS OCCURS AS SHOWN HERE 3065 02:44:44,560 --> 02:44:47,520 WHERE THE VES KELS THAT CONTAIN 3066 02:44:47,520 --> 02:44:49,120 NEUROPEPTIDES HAVE RELEASE 3067 02:44:49,120 --> 02:44:50,880 PATTERNS SO UNDER BASAL STATES 3068 02:44:50,880 --> 02:44:53,880 OR VERY LOW STRESS ONLY CERTAIN 3069 02:44:53,880 --> 02:44:55,600 GRANULES ARE RELEASED, 3070 02:44:55,600 --> 02:45:00,640 PARTICULARLY THOSE FOR CAT A A 3071 02:45:00,640 --> 02:45:03,280 COLEMAN BUT YOU UNDER THIS 3072 02:45:03,280 --> 02:45:04,840 DOESN'T REALLY SEEM TO FIT VERY 3073 02:45:04,840 --> 02:45:08,240 MUCH WITH THE FACT THAT SOME 3074 02:45:08,240 --> 02:45:10,480 NEURONS HAVE IN NEURO PEPTIDE 3075 02:45:10,480 --> 02:45:12,200 BUT INNERVATE THE HEART AND IN 3076 02:45:12,200 --> 02:45:13,880 ADDITION TO THAT IN PATIENTS 3077 02:45:13,880 --> 02:45:16,000 WITH SEVERE HEART FAILURE WE'VE 3078 02:45:16,000 --> 02:45:19,080 IDENTIFIED CIRCULATING LEVELS AS 3079 02:45:19,080 --> 02:45:21,280 WELL AS CORONARY SINUS LEVELS 3080 02:45:21,280 --> 02:45:24,360 AND LEVELS IN THE HEART AS BEING 3081 02:45:24,360 --> 02:45:25,880 PREDICTED OF PATIENTS WHO WILL 3082 02:45:25,880 --> 02:45:27,440 HAVE ADVERSE OUTCOMES. 3083 02:45:27,440 --> 02:45:31,400 FOR EXAMPLE, IF YOU SAMPLE 3084 02:45:31,400 --> 02:45:35,520 CORONARY SINUS NEURO PEPTIDE Y 3085 02:45:35,520 --> 02:45:36,120 LEVELS IN HAITIANS THEY'RE LOW 3086 02:45:36,120 --> 02:45:40,400 AND IF YOU LOOK AT PATIENTS WITH 3087 02:45:40,400 --> 02:45:42,880 INCREASES OF CARDIAC INJURY YOU 3088 02:45:42,880 --> 02:45:44,000 SEE THAT NERVE LEVELS ARE 3089 02:45:44,000 --> 02:45:45,880 DRAMATICALLY ELEVATED AND 3090 02:45:45,880 --> 02:45:47,640 FURTHER IF YOU ACTUALLY TAKE A 3091 02:45:47,640 --> 02:45:48,840 THRESHOLD APPROACH AND LOOK AT 3092 02:45:48,840 --> 02:45:50,560 PATIENTS WITH VERY HIGH NERVE 3093 02:45:50,560 --> 02:45:52,280 PEPTIDE Y LEVELS, MOST OF THOSE 3094 02:45:52,280 --> 02:45:54,240 PATIENTS WHO WERE STABLE, WERE 3095 02:45:54,240 --> 02:45:59,120 ALMOST DECEASED BY THROW AND A F 3096 02:45:59,120 --> 02:45:59,680 YEARS. 3097 02:45:59,680 --> 02:46:04,200 IT MADE US CRYSTALIZE ON NEURO 3098 02:46:04,200 --> 02:46:04,600 PEPTIDE Y. 3099 02:46:04,600 --> 02:46:06,440 TO VALIDATE THE SEQUENCING DATA 3100 02:46:06,440 --> 02:46:09,520 AND SHARE THAT IN DEED THERE ARE 3101 02:46:09,520 --> 02:46:10,120 NEWERRANCE THAT DO NOT EXPRESS 3102 02:46:10,120 --> 02:46:12,240 THAT INNERVATE THE HEART SO 3103 02:46:12,240 --> 02:46:15,600 THERE WAS A CLEVER EXPERIMENT 3104 02:46:15,600 --> 02:46:18,800 WHERE THEY COMBINED RETROGRADE 3105 02:46:18,800 --> 02:46:19,480 TRACING WITH SPACIAL TRACING 3106 02:46:19,480 --> 02:46:23,400 FROM THE HEART SO HE INJECTED 3107 02:46:23,400 --> 02:46:24,320 TWO DIFFERENT TRACERS AND TRACED 3108 02:46:24,320 --> 02:46:27,640 THEM BACK TO THE GANGLION TO 3109 02:46:27,640 --> 02:46:30,000 IDENTIFY ONE, THE SUBTYPES OF 3110 02:46:30,000 --> 02:46:32,000 NEURONS THAT INNERVATE THE HEART 3111 02:46:32,000 --> 02:46:36,560 AND THIS WAS DONE IN THE MPYGFT 3112 02:46:36,560 --> 02:46:39,160 ANIMAL AND LOOK AT THE 3113 02:46:39,160 --> 02:46:39,800 ESSENTIALLY THE SPACIAL CONTROL 3114 02:46:39,800 --> 02:46:41,800 IN THE HEART OF THE GANGLION. 3115 02:46:41,800 --> 02:46:44,600 AND SURE ENOUGH, THERE ARE 3116 02:46:44,600 --> 02:46:48,120 NEURONS SO GRO GREEN NEURONS HEE 3117 02:46:48,120 --> 02:46:51,440 HAVE MPY AND NEURONS THAT DO NOT 3118 02:46:51,440 --> 02:46:55,320 HAVE GFP DO NOT EXPRESS NPY AND 3119 02:46:55,320 --> 02:46:56,920 YOU CAN SEE IT FROM THE HEART 3120 02:46:56,920 --> 02:46:59,320 WHERE THEY DO NOT EXPRESS MPY AS 3121 02:46:59,320 --> 02:47:01,120 WELL AS NEURONS THAT DO 3122 02:47:01,120 --> 02:47:02,920 EXPRESSION MPY AND THE SAME FROM 3123 02:47:02,920 --> 02:47:04,760 THE BASE HERE IN BLUE, YOU SEE 3124 02:47:04,760 --> 02:47:06,560 THAT THERE ARE NEURONS THAT 3125 02:47:06,560 --> 02:47:09,080 AGAIN DO NOT HAVE ANY MPY BUT 3126 02:47:09,080 --> 02:47:10,240 INNERVATE THE HEART AS WELL AS 3127 02:47:10,240 --> 02:47:14,760 NEURONS THAT DO HAVE MPY SO IT'S 3128 02:47:14,760 --> 02:47:17,840 CORRECT THAT MPY AS WELL AS NPY 3129 02:47:17,840 --> 02:47:19,760 HIGH NEURONS INNERVATE THE 3130 02:47:19,760 --> 02:47:19,960 HEART. 3131 02:47:19,960 --> 02:47:21,560 IN ADDITION TO THAT WHEN WE 3132 02:47:21,560 --> 02:47:23,320 COMPARE THEM, WE FIND THAT MOST 3133 02:47:23,320 --> 02:47:25,640 NEURONS THAT INNERVATE THE HEART 3134 02:47:25,640 --> 02:47:27,720 EXPRESSION MPY BUT THERE'S A 3135 02:47:27,720 --> 02:47:29,360 PREPORTION THAT DON'T AND 3136 02:47:29,360 --> 02:47:30,920 INTERESTINGLY THE NEURONS THAT 3137 02:47:30,920 --> 02:47:33,400 EXPRESSION MPY AND INNERVATE THE 3138 02:47:33,400 --> 02:47:35,320 HEART ARE LARGER THAN THOSE THAT 3139 02:47:35,320 --> 02:47:36,000 DO NOT. 3140 02:47:36,000 --> 02:47:38,160 NEXT WE MOVED ON TO ELECTRO 3141 02:47:38,160 --> 02:47:39,960 PHYSICAL LOGIC PROFILING OF 3142 02:47:39,960 --> 02:47:41,480 THESE TWO DIFFERENT SUBTYPES 3143 02:47:41,480 --> 02:47:44,040 WHEN WE LOOKED AT THE TRANCE 3144 02:47:44,040 --> 02:47:46,040 SCRIP TOMB THERE ARE DIFFERENCES 3145 02:47:46,040 --> 02:47:49,280 IN SPECIFIC EXPRESSIONS SUCH AS 3146 02:47:49,280 --> 02:47:52,400 KSNQ AND THE 1A AND B SUBTYPES 3147 02:47:52,400 --> 02:47:55,600 OF THE CALCIUM CHANNELS AS WELL 3148 02:47:55,600 --> 02:47:56,680 AS CHLORIDE CHANNELS AND WE 3149 02:47:56,680 --> 02:48:00,320 PROFILED THIS USING AN IN VITRO 3150 02:48:00,320 --> 02:48:02,080 PREP AS SHOWN HERE WHERE WE CAN 3151 02:48:02,080 --> 02:48:04,680 TAKE THE ENTIRE GANGLION AND 3152 02:48:04,680 --> 02:48:06,200 REALLY PLUCK OUT A SINGLE NEURON 3153 02:48:06,200 --> 02:48:07,600 TO RECORD AND WE CAN BACK FILL 3154 02:48:07,600 --> 02:48:10,080 THOSE NEURONS WHEN WE'RE DONE 3155 02:48:10,080 --> 02:48:13,160 AND TO ESSENTIALLY LOCK AT THE 3156 02:48:13,160 --> 02:48:14,800 PROPERTIES AND VERIFY THAT WE 3157 02:48:14,800 --> 02:48:18,600 DID RECORD FROM A SINGLE NEURON 3158 02:48:18,600 --> 02:48:19,640 AND HERE ARE SOME OF THE 3159 02:48:19,640 --> 02:48:21,200 FINDINGS FROM THESE NEURONS 3160 02:48:21,200 --> 02:48:22,560 ESSENTIAL LOW LONG STORY SHORT 3161 02:48:22,560 --> 02:48:25,640 WE FIND THAT MPY HIGH NEURONS 3162 02:48:25,640 --> 02:48:27,520 ARE A LOT MORE EXCITE ABLE THAN 3163 02:48:27,520 --> 02:48:32,400 NEURONS THAT ARE LOW AND DO NOT 3164 02:48:32,400 --> 02:48:42,600 EXPRESS MPY. 3165 02:48:43,880 --> 02:48:47,200 IT WILL DRIVE A CRE DEPENDENT 3166 02:48:47,200 --> 02:48:48,880 EXPRESSION AND DELETE NEURONS AS 3167 02:48:48,880 --> 02:48:50,600 SHOWN HERE AND THEN WE INJECTED 3168 02:48:50,600 --> 02:48:52,640 A CONTROL VIRUS JUST EXPRESSING 3169 02:48:52,640 --> 02:48:54,520 GFP AND YOU CAN SEE THE 3170 02:48:54,520 --> 02:48:56,080 DIFFERENCES HERE AND AT BASELINE 3171 02:48:56,080 --> 02:48:56,600 INTERESTINGLY THERE'S NO 3172 02:48:56,600 --> 02:48:58,720 DIFFERENCE IN HEART RATES 3173 02:48:58,720 --> 02:49:00,840 SUGGESTING THAT NPY NEURONS ARE 3174 02:49:00,840 --> 02:49:02,680 NOT REQUIRED FOR BASAL HEART 3175 02:49:02,680 --> 02:49:08,880 RATE CONTROL AND THEN THEY PREP 3176 02:49:08,880 --> 02:49:10,960 RATED HERE STIMULATING THE GANG 3177 02:49:10,960 --> 02:49:12,840 LOW ON AND WE KNOW THESE NEURONS 3178 02:49:12,840 --> 02:49:14,520 INNERVATE THE HEART AND WE CAN 3179 02:49:14,520 --> 02:49:17,480 MEASURE HEART RATE AND WHAT WE 3180 02:49:17,480 --> 02:49:22,920 FIND IS THAT WHEN WE DELETE MPY 3181 02:49:22,920 --> 02:49:24,040 NEURONS, THESE ANIMALS JUST ARE 3182 02:49:24,040 --> 02:49:25,760 NOT ABLE TO GET THE HEART RATES 3183 02:49:25,760 --> 02:49:28,320 UP AS HIGH AND ESPECIALLY AS WE 3184 02:49:28,320 --> 02:49:30,360 ESCALATE THE STIMULATION 3185 02:49:30,360 --> 02:49:31,200 FREQUENCY. 3186 02:49:31,200 --> 02:49:32,840 SO, THIS PREPARATION HERE WOULD 3187 02:49:32,840 --> 02:49:34,680 MIMIC HIGH STATES OF SYMPATHETIC 3188 02:49:34,680 --> 02:49:36,640 STRESS AT HIGHER END OF 3189 02:49:36,640 --> 02:49:37,720 SYMPATHETIC STIMULATION AND 3190 02:49:37,720 --> 02:49:39,160 LOWER LEVELS OF SYMPATHETIC 3191 02:49:39,160 --> 02:49:41,960 STRESS AS THE LOWER LEVELS OF 3192 02:49:41,960 --> 02:49:43,720 STIMULATION SO CLEARLY IT LOOKS 3193 02:49:43,720 --> 02:49:49,760 LIKE MPY NEURONS ARE FOX MAXIMUM 3194 02:49:49,760 --> 02:49:49,960 STRESS. 3195 02:49:49,960 --> 02:49:51,760 YOU SAY YOU DELETED NEURONS IS 3196 02:49:51,760 --> 02:49:54,720 WHY IS IT THAT YOU WOULD EXPECT 3197 02:49:54,720 --> 02:49:57,560 MAXIMAL SYMPATHETIC STRESS SO 3198 02:49:57,560 --> 02:49:58,440 MAXIMAL RESPONSE SO WE LOOKED AT 3199 02:49:58,440 --> 02:50:03,640 THAT ASPECT OF THINGS AND MPY 3200 02:50:03,640 --> 02:50:08,120 MICE AND COMPARED THE KNOCK OUT 3201 02:50:08,120 --> 02:50:14,840 TO HOMO SIGH DO NOT HAVE NPY AND 3202 02:50:14,840 --> 02:50:15,880 WE ROW PETEED AND FOUND THAT IN 3203 02:50:15,880 --> 02:50:18,120 DEED THE LOSS OF MPY WAS 3204 02:50:18,120 --> 02:50:20,360 ASSOCIATED WITH THE INABILITY TO 3205 02:50:20,360 --> 02:50:22,160 ACHIEVE MAXIMUM SYMPATHETIC 3206 02:50:22,160 --> 02:50:22,520 STRESS. 3207 02:50:22,520 --> 02:50:24,440 AGAIN, WE WANTED TO ALSO REALLY 3208 02:50:24,440 --> 02:50:26,080 HONE IN ON THIS BECAUSE WE KNOW 3209 02:50:26,080 --> 02:50:29,480 THAT THE MPY1R RECEPTORS IS THE 3210 02:50:29,480 --> 02:50:32,000 MAJOR RECEPTORS FOR NEURO 3211 02:50:32,000 --> 02:50:33,160 PEPTIDE Y SIGNALING IN THE HEART 3212 02:50:33,160 --> 02:50:37,240 SO WE KNOCKED THAT OUTCOME 3213 02:50:37,240 --> 02:50:38,280 PAIRING HETERO SIGH GUS AND THE 3214 02:50:38,280 --> 02:50:40,320 SAME PREPARATION AND YOU SEE 3215 02:50:40,320 --> 02:50:48,960 THAT MICE NOW WITH THE HOMO SIGH 3216 02:50:48,960 --> 02:50:50,840 GUS DELETION COMPARED TO THE 3217 02:50:50,840 --> 02:50:52,760 DELETED ANIMALS. 3218 02:50:52,760 --> 02:50:54,120 SO WHAT THIS IS REALLY TELLING 3219 02:50:54,120 --> 02:50:56,720 US IS THAT AT LEAST IN THE 3220 02:50:56,720 --> 02:50:58,520 DESCENDING LYMPH THIS CIRCUIT 3221 02:50:58,520 --> 02:51:02,880 CONTROL IS THAT THERE'S TIERED 3222 02:51:02,880 --> 02:51:07,200 CONTROL BY THE NEURONS WHERE AT 3223 02:51:07,200 --> 02:51:14,280 LOW LEVELS OF WHEN HIGHER 3224 02:51:14,280 --> 02:51:15,240 CITATION IS NEEDED IT'S 3225 02:51:15,240 --> 02:51:17,640 CONTROLLED BY DIFFERENT SUBTYPES 3226 02:51:17,640 --> 02:51:21,040 OF CELLS AND NA1 AND NA3 IN 3227 02:51:21,040 --> 02:51:23,760 PREPARATION SO I'LL STOP BY 3228 02:51:23,760 --> 02:51:25,320 SUMMARIZING WE FIND THREE 3229 02:51:25,320 --> 02:51:28,520 SUBTYPES OF SYMPATHETIC NEURONS 3230 02:51:28,520 --> 02:51:32,480 AND THEY APPEAR CONSERVED ACROSS 3231 02:51:32,480 --> 02:51:34,760 MOUSE AND UNIQUE AND ELECTRIC 3232 02:51:34,760 --> 02:51:35,760 PHYSICAL LOGIC PROPERTIES AND 3233 02:51:35,760 --> 02:51:41,200 THEY APPEAR TO BE FUNCTION IN 3234 02:51:41,200 --> 02:51:43,040 TIERED CONTROL MANNER WHERE ONE 3235 02:51:43,040 --> 02:51:46,360 SUBTYPE OF NEURONS MEDIATES THE 3236 02:51:46,360 --> 02:51:50,280 LOW CITATION AND TWO OTHER 3237 02:51:50,280 --> 02:51:51,880 SUBTYPES MEDIATE HIGH CITATIONS 3238 02:51:51,880 --> 02:51:54,280 AND WITH THAT I'LL STOP AND 3239 02:51:54,280 --> 02:51:55,840 ACKNOWLEDGE MY COLLEAGUES AT 3240 02:51:55,840 --> 02:51:57,240 UCLA AND THE MEMBERS OF MY LAB 3241 02:51:57,240 --> 02:52:01,160 THAT DO THIS. 3242 02:52:01,160 --> 02:52:01,560 THANK YOU. 3243 02:52:01,560 --> 02:52:06,280 [APPLAUSE] 3244 02:52:06,280 --> 02:52:07,400 >>THANK YOU, VERY MUCH. 3245 02:52:07,400 --> 02:52:08,480 WE'LL TAKE ONE QUESTION AND 3246 02:52:08,480 --> 02:52:12,120 WE'LL MOVE TO A GENERAL Q&A 3247 02:52:12,120 --> 02:52:12,360 SESSION. 3248 02:52:12,360 --> 02:52:13,560 DOES ANYONE HAVE ANY QUESTIONS 3249 02:52:13,560 --> 02:52:16,600 IN THE ROOM FIRST? 3250 02:52:16,600 --> 02:52:18,080 >>VERY NICE PRESENTATION. 3251 02:52:18,080 --> 02:52:19,280 I'M A LITTLE BIT SURPRISED THAT 3252 02:52:19,280 --> 02:52:25,200 YOU DID NOT LOOK INTO INNOVATION 3253 02:52:25,200 --> 02:52:25,760 OF ARTERIES. 3254 02:52:25,760 --> 02:52:28,200 I KNOW THAT MPY IS VERY WELL 3255 02:52:28,200 --> 02:52:31,120 KNOWN TO GO WITH ARTERY 3256 02:52:31,120 --> 02:52:32,400 INNOVATION SO DID YOU EXCLUDE 3257 02:52:32,400 --> 02:52:32,600 THAT? 3258 02:52:32,600 --> 02:52:35,720 >>NO, WE DIDN'T. 3259 02:52:35,720 --> 02:52:37,960 WE WERE JUST FOCUSED FOR OUR 3260 02:52:37,960 --> 02:52:39,520 INITIAL STUDIES JUST ON HEART 3261 02:52:39,520 --> 02:52:41,640 RATE CONTROL BUT YOU ARE 3262 02:52:41,640 --> 02:52:44,400 ABSOLUTELY RIGHT THAT MPY 3263 02:52:44,400 --> 02:52:46,880 NEURONS DO DENSELY INTER RATE IS 3264 02:52:46,880 --> 02:52:48,640 ARTERIES AND THAT WILL BE THE 3265 02:52:48,640 --> 02:52:50,280 FOCUS OF A FUTURE WORK BUT 3266 02:52:50,280 --> 02:52:52,040 PARTICULARLY WE'RE JUST LOOKING 3267 02:52:52,040 --> 02:52:55,320 HERE AT CONTROL OF THE HEART. 3268 02:52:55,320 --> 02:52:55,920 THANK YOU. 3269 02:52:55,920 --> 02:52:57,240 >>I THINK WE HAD ANOTHER 3270 02:52:57,240 --> 02:52:58,200 QUESTION FOR YOU. 3271 02:52:58,200 --> 02:53:01,240 WHILE YOU ARE HERE. 3272 02:53:01,240 --> 02:53:05,040 >>IT'S NOT TOTALLY DIRECTLY TO 3273 02:53:05,040 --> 02:53:08,760 YOUR TALK BUT ONE OF THE MAIN 3274 02:53:08,760 --> 02:53:10,840 INTRO ACCEPTIVE TASKS IN HUMANS 3275 02:53:10,840 --> 02:53:16,200 IS TO ASK THEM TO COUNT THEIR 3276 02:53:16,200 --> 02:53:26,520 HEART BEATS RIGHT. 3277 02:53:29,240 --> 02:53:35,280 >>WE CAN ACTUALLY TARGET THE 3278 02:53:35,280 --> 02:53:37,520 SPINAL SYMPATHETIC PATHWAY WITH 3279 02:53:37,520 --> 02:53:40,240 OUR SYMPATHETIC IN PATIENTS SO 3280 02:53:40,240 --> 02:53:43,600 THE ANSWER TO THAT IS TBD. 3281 02:53:43,600 --> 02:53:48,680 I DO SUSPECT THAT BOTH THE VAGAL 3282 02:53:48,680 --> 02:53:50,360 PATHWAY AND SPINAL PATHWAYS ARE 3283 02:53:50,360 --> 02:53:52,120 IMPORTANT BUT THE CON TRIB 3284 02:53:52,120 --> 02:54:02,040 BUYINGS OF ONE RCON INTETHEY WI. 3285 02:54:02,040 --> 02:54:04,240 >>DOES ANYONE HAVE QUESTIONS 3286 02:54:04,240 --> 02:54:05,640 FOR THE FOUR SPEAKERS IN THIS 3287 02:54:05,640 --> 02:54:06,720 SESSION IN THE ROOM? 3288 02:54:06,720 --> 02:54:11,600 >>IF NOT, PLEASE. 3289 02:54:11,600 --> 02:54:12,760 >>FIRST, THANK YOU FOR ALL THE 3290 02:54:12,760 --> 02:54:14,200 GREAT TALKS AND REALLY I'M 3291 02:54:14,200 --> 02:54:16,000 LEARNING SO MUCH AND I REALLY 3292 02:54:16,000 --> 02:54:19,960 ENJOYED IT AND THIS IS A 3293 02:54:19,960 --> 02:54:23,040 QUESTION FOR THE TWO LUNG 3294 02:54:23,040 --> 02:54:23,400 SPEAKERS. 3295 02:54:23,400 --> 02:54:25,400 WHAT I'M THINKING ABOUT WHEN 3296 02:54:25,400 --> 02:54:31,640 LISTENING TO YOUR TALKS IS 3297 02:54:31,640 --> 02:54:31,840 COVID. 3298 02:54:31,840 --> 02:54:35,840 HOW COULD THE VIRUS IN THE LUNG 3299 02:54:35,840 --> 02:54:38,000 POTENTIALLY AFFECT THE BRAIN AND 3300 02:54:38,000 --> 02:54:43,080 HAVE AN IMPACT ON BEHAVIOR ON 3301 02:54:43,080 --> 02:54:44,440 NEWER LOGIC FUNCTION SO ARE 3302 02:54:44,440 --> 02:54:45,720 THERE ROOTS THAT YOU THOUGHT 3303 02:54:45,720 --> 02:54:47,520 ABOUT OR MECHANISMS BY WHICH 3304 02:54:47,520 --> 02:54:53,760 THIS COULD OCCUR? 3305 02:54:53,760 --> 02:54:59,200 >>SO, ACTUALLY, WITH WEN WE 3306 02:54:59,200 --> 02:55:00,920 HAVE A COVID SUPPLEMENT ON THIS 3307 02:55:00,920 --> 02:55:03,000 GRANT LOOKING AT EXACTLY THAT, 3308 02:55:03,000 --> 02:55:05,400 ESPECIALLY LONG COVID RESPONSES. 3309 02:55:05,400 --> 02:55:06,800 WHETHER IT'S A INFECTION IN THE 3310 02:55:06,800 --> 02:55:08,120 BRAIN OR WHETHER IT'S INFECTION 3311 02:55:08,120 --> 02:55:09,880 IN THE LUNG AND OTHER INTERNAL 3312 02:55:09,880 --> 02:55:12,520 ORGANS THAT GETS TRANSMITTED TO 3313 02:55:12,520 --> 02:55:14,280 THE BRAIN THROUGH THE VAGAL 3314 02:55:14,280 --> 02:55:15,320 NEURONS SO ACTUALLY THE OTHER 3315 02:55:15,320 --> 02:55:20,080 PART OF MY LAB WORK ON LUNG STEM 3316 02:55:20,080 --> 02:55:21,520 CELL ACTIVATION AFTER INJURY 3317 02:55:21,520 --> 02:55:23,160 RESPONSE SO WE HAVE THOSE 3318 02:55:23,160 --> 02:55:25,160 WORKING ON THE COVID MOUSE MODEL 3319 02:55:25,160 --> 02:55:26,720 BUT WE HAVE THE FLU MODEL THAT 3320 02:55:26,720 --> 02:55:32,000 WE'RE STARTING TO WORK ON. 3321 02:55:32,000 --> 02:55:36,000 >>SO, NICK WHO WORKS WITH Dr. 3322 02:55:36,000 --> 02:55:37,440 BLOOD AND Dr. SUN AND I HAVE 3323 02:55:37,440 --> 02:55:39,240 SHOWN THERE'S ACE 2 IN THE COR 3324 02:55:39,240 --> 02:55:41,240 OTED BODY AND THE NTS SO THAT 3325 02:55:41,240 --> 02:55:42,400 VECTOR FOR COVID TO GET INTO 3326 02:55:42,400 --> 02:55:44,720 THOSE CELLS IS THERE. 3327 02:55:44,720 --> 02:55:46,200 THERE MAY BE CHANGES IT'S 3328 02:55:46,200 --> 02:55:47,480 SOMETHING WE'RE STILL WORKING ON 3329 02:55:47,480 --> 02:55:51,920 WITH ANOTHER COLLEAGUE AT UCSD 3330 02:55:51,920 --> 02:55:52,680 ON BRAIN. 3331 02:55:52,680 --> 02:55:54,200 GAINING TO THAT CIRCUIT WOULD 3332 02:55:54,200 --> 02:55:55,440 ALTER BREATHING CONTROL. 3333 02:55:55,440 --> 02:55:59,920 >>YEAH AND I WANT TO ADD THAT 3334 02:55:59,920 --> 02:56:00,760 APPARENTLY COUGH IS ONE OF THE 3335 02:56:00,760 --> 02:56:03,880 MAJOR SYMPTOMS OF COVID AND NOW 3336 02:56:03,880 --> 02:56:06,360 WE ARE NOT WORKING ON THE COVID 3337 02:56:06,360 --> 02:56:08,680 MODELEL YET BUT WHEN WE PICK OPT 3338 02:56:08,680 --> 02:56:15,240 CIRCUIT, IT'S WORTH CHECKING HOW 3339 02:56:15,240 --> 02:56:16,120 IT'S EFFECTING. 3340 02:56:16,120 --> 02:56:16,360 >> 3341 02:56:16,360 --> 02:56:24,200 >>SO MAYBE, A QUESTION FOR ALL 3342 02:56:24,200 --> 02:56:29,240 BUT MAYBE, THEY COULD START AND 3343 02:56:29,240 --> 02:56:30,880 ABOUT THE GRANULARITY OF CONTROL 3344 02:56:30,880 --> 02:56:36,240 SO WE SAW IN TWO TALKS, FOR 3345 02:56:36,240 --> 02:56:39,040 EXAMPLE, DIFFERENT POPULATIONS 3346 02:56:39,040 --> 02:56:42,240 CONTROLLING DIFFERENT RESPONSES 3347 02:56:42,240 --> 02:56:44,520 OF SIMILAR MUSCLES SO I MEAN, 3348 02:56:44,520 --> 02:56:45,880 THERE'S A SENSORY ASPECT THAT 3349 02:56:45,880 --> 02:56:47,480 YOU ARE FOCUSING BUT THE 3350 02:56:47,480 --> 02:56:50,600 RESPONSE ASPECTS AND THEN WE SAW 3351 02:56:50,600 --> 02:56:53,200 IN THE SYMPATHETIC, I MEAN 3352 02:56:53,200 --> 02:56:54,960 THERE'S LOW AND HIGH BUT THEY 3353 02:56:54,960 --> 02:57:00,360 COULD BE MODULATING DIFFERENT 3354 02:57:00,360 --> 02:57:06,160 PHYSIOLOGICAL RESPONSES SO 3355 02:57:06,160 --> 02:57:07,600 THERE'S MUCH MORE GRANULARITY IN 3356 02:57:07,600 --> 02:57:09,760 THE SYSTEM IN TERMS OF NOT ONLY 3357 02:57:09,760 --> 02:57:12,000 SPECIFIC SENSING BUT SPECIFIC 3358 02:57:12,000 --> 02:57:14,800 CONTROL OF THE RESPONSES. 3359 02:57:14,800 --> 02:57:17,680 WOULD YOU COMMENT ON THIS? 3360 02:57:17,680 --> 02:57:21,000 >>YEAH, I THINK IN TERMS OF 3361 02:57:21,000 --> 02:57:24,200 BREATHING, MANY OF THE MUSCLES 3362 02:57:24,200 --> 02:57:25,760 ARE SHARED BY DIFFERENT BEHAVE 3363 02:57:25,760 --> 02:57:28,400 YEARS INCLUDING BREATHING AND 3364 02:57:28,400 --> 02:57:31,520 AWE RESPIRATORY RELATED 3365 02:57:31,520 --> 02:57:35,600 BEHAVIORS OR VOCALIZATIONS AND 3366 02:57:35,600 --> 02:57:36,440 ALL THE CRANIAL FACIAL FUNCTIONS 3367 02:57:36,440 --> 02:57:38,320 SO REALLY UNDERSTANDING LIKE 3368 02:57:38,320 --> 02:57:41,080 WHAT ARE THE MOTOR CONTROLS 3369 02:57:41,080 --> 02:57:42,960 MODULES OF THESE BEHAVIORS WOULD 3370 02:57:42,960 --> 02:57:45,160 BE VERY IMPORTANT AND IT THEN I 3371 02:57:45,160 --> 02:57:49,560 THINK THAT WILL ALSO PROVIDE US 3372 02:57:49,560 --> 02:57:52,160 PARADIGM LIKE HOW EVOLUTIONARY 3373 02:57:52,160 --> 02:57:54,320 WE DEVELOPED THIS NEUROCIRCUITS 3374 02:57:54,320 --> 02:57:57,880 USING THE SAME KIND OF MUSCLE 3375 02:57:57,880 --> 02:58:00,360 AND MOTOR OUTPUT AND COMBINE 3376 02:58:00,360 --> 02:58:02,120 THEM TOGETHER AND TO GENERATE A 3377 02:58:02,120 --> 02:58:07,120 DIFFERENT PATTERN. 3378 02:58:07,120 --> 02:58:09,080 >>I THINK IT'S A FASCINATING 3379 02:58:09,080 --> 02:58:09,320 QUESTION. 3380 02:58:09,320 --> 02:58:11,240 FOR THE HEART, IT'S ACTUALLY 3381 02:58:11,240 --> 02:58:12,560 PARTICULARLY IMPORTANT AND 3382 02:58:12,560 --> 02:58:13,880 EXACTLY WHAT ARE SAYING BECAUSE 3383 02:58:13,880 --> 02:58:16,360 THE HEART REQUIRES THIS VERY 3384 02:58:16,360 --> 02:58:19,120 HIGHLY COORDINATED PATTERN OF 3385 02:58:19,120 --> 02:58:21,360 CONTRACTION AND ELECTRICAL 3386 02:58:21,360 --> 02:58:22,200 PROPAGATION AND THAT'S ONE OF 3387 02:58:22,200 --> 02:58:23,400 THE REASONS WE'RE INTERESTED IN 3388 02:58:23,400 --> 02:58:25,040 THIS AREA IS THAT THE SUDDEN 3389 02:58:25,040 --> 02:58:26,520 CHANGE IN ELECTRICAL PROPERTIES 3390 02:58:26,520 --> 02:58:27,880 OF THE HEART CAN ACTUALLY LEAD 3391 02:58:27,880 --> 02:58:29,760 TO SUDDEN DEATH SO IT'S ONE OF 3392 02:58:29,760 --> 02:58:32,280 THE MECHANISMS OF DEATH THAT 3393 02:58:32,280 --> 02:58:33,160 WORE INTERESTED IN. 3394 02:58:33,160 --> 02:58:34,480 I COMPLETELY AGREE WITH YOU. 3395 02:58:34,480 --> 02:58:36,920 I THINK IT'S SOMETHING THAT WE 3396 02:58:36,920 --> 02:58:38,640 REALLY NEED TO PROBE IS TO 3397 02:58:38,640 --> 02:58:43,000 ACTUALLY LOOK AT DIFFERENT WAYS 3398 02:58:43,000 --> 02:58:44,320 OF, I DON'T WANT TO SAY INJURY 3399 02:58:44,320 --> 02:58:45,960 TO THE HEART BUT DIFFERENT 3400 02:58:45,960 --> 02:58:47,360 STIMULI TO THE HEART SO THINGS 3401 02:58:47,360 --> 02:58:50,080 LIKE EITHER ISCHEMIA OR 3402 02:58:50,080 --> 02:58:56,840 SIMULATING AN AN ARRHYTHMIA ANDE 3403 02:58:56,840 --> 02:58:58,480 WHETHER THEY MEDIATE THAT SORT 3404 02:58:58,480 --> 02:59:03,720 OF RESPONSE BACK DOWN TO THE 3405 02:59:03,720 --> 02:59:04,080 HEART. 3406 02:59:04,080 --> 02:59:04,920 OTHER QUESTIONS FROM THE ROOM? 3407 02:59:04,920 --> 02:59:08,320 >>CAN I ANSWER THAT FURTHER? 3408 02:59:08,320 --> 02:59:11,840 WHEN YOU TALK ABOUT GRANULARITY 3409 02:59:11,840 --> 02:59:13,040 YOU HAVE BREATH TO BREATH AND 3410 02:59:13,040 --> 02:59:15,680 BEAT TO BEAT BUT COUGH IS THE 3411 02:59:15,680 --> 02:59:16,840 DIAPHRAGM INVOLVED BUT YOU HAVE 3412 02:59:16,840 --> 02:59:18,400 INCOMPETENTER COSTAL INVOLVEMENT 3413 02:59:18,400 --> 02:59:19,560 AS WELL AND YOU HAVE TO BE ABLE 3414 02:59:19,560 --> 02:59:21,120 TO CONTROL THAT SUITE OF MUSCLE 3415 02:59:21,120 --> 02:59:22,880 ACTIVITY IN ORDER TO GET THE PRO 3416 02:59:22,880 --> 02:59:25,000 PRO AT RESPONSE FOR A NORMAL 3417 02:59:25,000 --> 02:59:26,080 SIGH OR COUGH OR SOMETHING LIKE 3418 02:59:26,080 --> 02:59:30,160 THAT SO IT'S HIGHLY CONTROLLED. 3419 02:59:30,160 --> 02:59:31,680 RAPIDLY ADAPTING RECEPTORS FROM 3420 02:59:31,680 --> 02:59:34,200 THE LUNG CAN PROVIDE 3421 02:59:34,200 --> 02:59:35,160 BREATH-TO-BREATH CONTROL AND 3422 02:59:35,160 --> 02:59:37,200 DEPTH OF INSPIRATION AND OF 3423 02:59:37,200 --> 02:59:40,480 COURSE WE GET BREATH-TO-BREATH 3424 02:59:40,480 --> 02:59:42,120 CONTROL AND IT DRYS RESPIRATORY 3425 02:59:42,120 --> 02:59:44,320 RHYTHM SO IT'S GRANULAR AND 3426 02:59:44,320 --> 02:59:44,680 HIGHLY DETAILED. 3427 02:59:44,680 --> 02:59:46,840 >>I JUST WANTED TO ADD ON TOP 3428 02:59:46,840 --> 02:59:50,120 OF THAT WITH THE REPEATED INPUT 3429 02:59:50,120 --> 02:59:51,440 AND THERE'S ADAPTATION THAT 3430 02:59:51,440 --> 02:59:56,400 COULD CHANGE ON THE LEVEL OF 3431 02:59:56,400 --> 02:59:59,280 CONNECTIVITY AND TRANSCRIPTIONAL 3432 02:59:59,280 --> 03:00:02,120 DIFFERENCES OF TRANSMITTERS AND 3433 03:00:02,120 --> 03:00:05,200 RECEPTORS THAT COULD ACT AS THE 3434 03:00:05,200 --> 03:00:07,080 DIVERSITY AND SPECIFICITY. 3435 03:00:07,080 --> 03:00:09,200 >>LET ME ADD ONE OTHER THING, 3436 03:00:09,200 --> 03:00:11,200 NOT TO GO THE OTHER WAY BUT JUST 3437 03:00:11,200 --> 03:00:14,080 SORT OF TO PLAY DEVIL'S ADVOCATE 3438 03:00:14,080 --> 03:00:16,520 IS THROUGH AT LEAST ON THE 3439 03:00:16,520 --> 03:00:18,320 SYMPATHETIC SIDE OF THINGS THE 3440 03:00:18,320 --> 03:00:19,360 COORDINATION BETWEEN THE HEART 3441 03:00:19,360 --> 03:00:22,160 AND THE LUNGS WAS ACTUALLY IN 3442 03:00:22,160 --> 03:00:24,080 SOME LARGE ANIMAL EXPERIMENTS WE 3443 03:00:24,080 --> 03:00:26,080 DID WHERE WE WERE RECORDING FROM 3444 03:00:26,080 --> 03:00:28,720 THE GANGLION AND LOOKING AT 3445 03:00:28,720 --> 03:00:30,480 SINGLE-UNIT AND MULTI-UNIT 3446 03:00:30,480 --> 03:00:31,960 ACTIVITY, THEY WERE STRUCK BY 3447 03:00:31,960 --> 03:00:34,800 HOW MUCH MODULATION OF NEURONS 3448 03:00:34,800 --> 03:00:38,240 THAT INTENDED TO RESPOND TO 3449 03:00:38,240 --> 03:00:39,640 CARDIAC ACTIVITY BY LUNG 3450 03:00:39,640 --> 03:00:41,320 FUNCTION SO ALTHOUGH THERE'S 3451 03:00:41,320 --> 03:00:44,160 THIS VERY GRANULAR CONTROL SORT 3452 03:00:44,160 --> 03:00:45,920 OF AT A HIGH LEVEL OF THESE 3453 03:00:45,920 --> 03:00:47,920 SYSTEMS ARE STILL VERY HIGHLY 3454 03:00:47,920 --> 03:00:51,920 INTEGRATED AND I THINK THAT THE 3455 03:00:51,920 --> 03:00:52,920 SYSTEM DOES RECOGNIZE THIS SORT 3456 03:00:52,920 --> 03:00:58,520 OF DIS CO DINNATED ACTIVITY. 3457 03:00:58,520 --> 03:01:00,240 >>WE HAVE TIME FOR ONE MORE 3458 03:01:00,240 --> 03:01:04,400 QUESTION AND WE'LL TAKE IT FROM 3459 03:01:04,400 --> 03:01:07,600 THE CHAT. 3460 03:01:07,600 --> 03:01:09,480 Dr. BLOOD AND WILSON ARE 3461 03:01:09,480 --> 03:01:11,640 ASKED, ANALOGOUS HEART, WHAT ARE 3462 03:01:11,640 --> 03:01:14,080 THE REGULATORY FUNCTIONS OF THE 3463 03:01:14,080 --> 03:01:18,000 INTRINSIC NEUROCIRCUITS OF LUNG? 3464 03:01:18,000 --> 03:01:21,920 >>YEAH, WE'D LIKE TO FIGURE 3465 03:01:21,920 --> 03:01:22,520 THAT OUT. 3466 03:01:22,520 --> 03:01:23,920 IF YOU THINK ABOUT AIRWAY 3467 03:01:23,920 --> 03:01:25,920 CONTROL AND SMOOTH MUSCLE TONE, 3468 03:01:25,920 --> 03:01:28,280 IN THE UPPER AIRWAYS, THAT IS 3469 03:01:28,280 --> 03:01:29,480 SOMETHING THAT IS PROBABLY 3470 03:01:29,480 --> 03:01:31,120 CLOSELY REGULATED AND THIS IS 3471 03:01:31,120 --> 03:01:32,640 SOMETHING THAT DOCTOR SUN AND 3472 03:01:32,640 --> 03:01:34,560 Dr. BLOOD AND I HAVE TALKED 3473 03:01:34,560 --> 03:01:36,000 ABOUT TRYING TO EXPLORE FURTHER. 3474 03:01:36,000 --> 03:01:39,760 WHEN IT IT COMES TO INS INSCEPTI 3475 03:01:39,760 --> 03:01:41,560 DON'T KNOW THAT ANYBODY KNOWS 3476 03:01:41,560 --> 03:01:42,520 THAT WHETHER OR NOT THERE'S AN 3477 03:01:42,520 --> 03:01:43,520 IMPACT SO IT'S SOMETHING THAT 3478 03:01:43,520 --> 03:01:45,600 WOULD BE FASCINATING TO PURSUE. 3479 03:01:45,600 --> 03:01:46,640 GREAT QUESTION FROM JEFF. 3480 03:01:46,640 --> 03:01:48,040 >>SO I THINK ANY OTHER 3481 03:01:48,040 --> 03:01:49,240 QUESTIONS AND THE CHAT WE WILL 3482 03:01:49,240 --> 03:01:52,400 RELAY TO THE SPEAKERS AND MOVE 3483 03:01:52,400 --> 03:01:57,040 ONTO THE NEXT SESSION AND. 3484 03:01:57,040 --> 03:01:59,080 >>GREAT, THANK YOU, IT'S MY 3485 03:01:59,080 --> 03:02:00,640 PLEASURE AND HONOR TO MODERATE 3486 03:02:00,640 --> 03:02:02,440 THIS SESSION AND SESSION 3, 3487 03:02:02,440 --> 03:02:04,960 METABOLIC IMMUNE MUSS YOU LAR 3488 03:02:04,960 --> 03:02:06,720 AND BRAIN CONNECTIONS. 3489 03:02:06,720 --> 03:02:08,480 OUR SPEAKERS I'LL JUST READ THEM 3490 03:02:08,480 --> 03:02:18,960 OUT AND THEY'RE TALKS -- AND 3491 03:02:19,400 --> 03:02:20,680 CHUNG FROM UNIVERSITY OF TEXAS 3492 03:02:20,680 --> 03:02:22,720 AND UNIVERSITY OF MARYLAND AND 3493 03:02:22,720 --> 03:02:29,880 BOLT MORE RESPECTIVELY AND Dr. 3494 03:02:29,880 --> 03:02:40,040 COSTA AND. 3495 03:03:58,600 --> 03:04:00,240 >>IT DEPENDS ON THE INTERNAL 3496 03:04:00,240 --> 03:04:01,680 STATE OF THE BODY AND WHETHER OR 3497 03:04:01,680 --> 03:04:05,920 NOT THOSE OBJECTS ARE VALUABLE. 3498 03:04:05,920 --> 03:04:08,160 IT'S A SITE OF SENSORY INPUTS 3499 03:04:08,160 --> 03:04:12,080 FROM THE BODY BOTH SPINAL AND 3500 03:04:12,080 --> 03:04:18,680 VAGAL AND OTHER AND SO AN 3501 03:04:18,680 --> 03:04:20,800 IMPORTANT THEORY FROM THE DRUG 3502 03:04:20,800 --> 03:04:23,720 ADDICTION LITERATURE TRIED TO 3503 03:04:23,720 --> 03:04:25,480 INTEGRATE THESE TOGETHER AND IN 3504 03:04:25,480 --> 03:04:27,160 THE CONTEXT OF THINKING ABOUT 3505 03:04:27,160 --> 03:04:29,640 FEEDING AND DRINKING, ONE THING 3506 03:04:29,640 --> 03:04:31,440 THAT IT MIGHT BE DOING IS 3507 03:04:31,440 --> 03:04:35,160 CREATING A PREDICTION OF FUTURE 3508 03:04:35,160 --> 03:04:35,760 PHYSIOLOGICAL STATES. 3509 03:04:35,760 --> 03:04:37,320 SO IN PARTICULAR, HOW WILL 3510 03:04:37,320 --> 03:04:39,240 EATING THIS FOOD OR DRINKING 3511 03:04:39,240 --> 03:04:43,080 THIS WATER MAKE ME FEEL? 3512 03:04:43,080 --> 03:04:44,720 AND WE WANTED TO ADDRESS THIS 3513 03:04:44,720 --> 03:04:46,520 QUESTION IN OUR STUDIES IN MICE 3514 03:04:46,520 --> 03:04:51,120 AND THE WORK WAS LED BY A FORMER 3515 03:04:51,120 --> 03:04:52,560 POSTDOC IN THE LAB AND CARRIED 3516 03:04:52,560 --> 03:04:55,360 ON BY SEVERAL OTHERS IN THE LAB. 3517 03:04:55,360 --> 03:04:59,080 I'M GOING TO FOCUS FIRST ON FOOD 3518 03:04:59,080 --> 03:05:01,280 CRUISE IN THE MOUSE A VISUAL 3519 03:05:01,280 --> 03:05:04,520 FOOD CREW HAS TO BE TRAINED. 3520 03:05:04,520 --> 03:05:06,040 WE TRAIN THE MOUSE AND ONE 3521 03:05:06,040 --> 03:05:07,400 PICTURE IS ASSOCIATED WITH FOOD 3522 03:05:07,400 --> 03:05:10,240 AND IN THIS CASE A DROP OF MILK 3523 03:05:10,240 --> 03:05:12,040 SHARE AND ANOTHER PICTURE MEANS 3524 03:05:12,040 --> 03:05:13,080 NOTHING WILL HAPPEN AND THE MICE 3525 03:05:13,080 --> 03:05:14,960 LEARN THAT WHEN THEY SEE ONE 3526 03:05:14,960 --> 03:05:16,600 PICTURE, THEY START TO LICK IN 3527 03:05:16,600 --> 03:05:17,840 RESPONSE TO THAT PICTURE TO 3528 03:05:17,840 --> 03:05:21,880 INDICATE THEY WANT THE FOOD AND 3529 03:05:21,880 --> 03:05:23,360 THEY WILL EAT SEVERAL MILL 3530 03:05:23,360 --> 03:05:27,160 LITERS AND THEY'LL JUST STOP 3531 03:05:27,160 --> 03:05:31,480 RESPONDING AND IF YOU SILENCE 3532 03:05:31,480 --> 03:05:33,280 INSULAR CORTEX WHAT YOU FIND IS 3533 03:05:33,280 --> 03:05:35,480 THAT WHILE IT ABOLISHES THIS 3534 03:05:35,480 --> 03:05:37,520 BEHAVIOR ENTIRELY, WE WERE 3535 03:05:37,520 --> 03:05:40,240 SURPRISED THAT IT REALLY DIDN'T 3536 03:05:40,240 --> 03:05:40,840 EFFECT HOME CAGE FEEDING AND IT 3537 03:05:40,840 --> 03:05:42,120 DIDN'T EVEN EFFECT THE 3538 03:05:42,120 --> 03:05:44,440 CONSUMPTION OF THE SAME MILK 3539 03:05:44,440 --> 03:05:46,400 SHAKE WHEN IT WASN'T ASSOCIATED 3540 03:05:46,400 --> 03:05:48,040 WITH ANY LEARNED CUES SO WE 3541 03:05:48,040 --> 03:05:50,920 REALLY THINK THAT THE CONTROL OF 3542 03:05:50,920 --> 03:05:53,400 THE INSULAR CORTEX AS AN 3543 03:05:53,400 --> 03:05:55,360 ADDITIONAL LAYER ON TOP OF THE 3544 03:05:55,360 --> 03:05:56,760 STUDIES PEOPLE HAVE DEMONSTRATED 3545 03:05:56,760 --> 03:05:58,640 TODAY MIGHT BE A PLACE THAT'S 3546 03:05:58,640 --> 03:06:00,880 IMPORTANT FOR LEARNED 3547 03:06:00,880 --> 03:06:02,360 ASSOCIATIONS AND PREDICTIONS OF 3548 03:06:02,360 --> 03:06:04,960 FUTURE OUTCOMES. 3549 03:06:04,960 --> 03:06:06,480 NOW TO GET A BETTER SENSE OF 3550 03:06:06,480 --> 03:06:07,920 WHETHER THAT MIGHT BE THE CASE, 3551 03:06:07,920 --> 03:06:10,400 WE WANTED TO RECORD FROM THE 3552 03:06:10,400 --> 03:06:13,200 NEURONS AND INSULAR CORTEX SO 3553 03:06:13,200 --> 03:06:14,800 YOU HAVE ANOTHERS THAT DEVELOPED 3554 03:06:14,800 --> 03:06:18,320 A PARA SCOPE APPROACH WHERE WE 3555 03:06:18,320 --> 03:06:23,520 COULD USE CUL CALCIUM IMAGING A 3556 03:06:23,520 --> 03:06:24,120 WAKE HOUSE. 3557 03:06:24,120 --> 03:06:26,120 I'LL SHOW YOU AN INDIVIDUAL 3558 03:06:26,120 --> 03:06:28,040 NEURON AND INSULAR CORTEX IN 3559 03:06:28,040 --> 03:06:29,200 RESPONSE TO THE PRESENTATION OF 3560 03:06:29,200 --> 03:06:31,760 A FOOD CUE, YOU CAN SEE THIS 3561 03:06:31,760 --> 03:06:33,360 NEURON IN ORANGE IS INCREASING 3562 03:06:33,360 --> 03:06:35,760 ITS ACTIVITY AS THE FOOD CUE IS 3563 03:06:35,760 --> 03:06:36,800 PRESENTED WHEN THE MOUSE IS 3564 03:06:36,800 --> 03:06:39,400 HUNGRY BUT AFTER THE MOUSE 3565 03:06:39,400 --> 03:06:43,120 BECOMES SATED THE SAME NEURON NO 3566 03:06:43,120 --> 03:06:44,880 LONGER RESPONDS TO THE FOOD. 3567 03:06:44,880 --> 03:06:49,040 IN EARLY PRIMARY VISUAL CORTEX 3568 03:06:49,040 --> 03:06:51,200 WHERE THE VISUAL CUES MATTER THE 3569 03:06:51,200 --> 03:06:52,280 RESPONSES ARE SIMILAR WHETHER OR 3570 03:06:52,280 --> 03:06:56,280 NOT THE MOUSE IS HUNGRY OR 3571 03:06:56,280 --> 03:06:56,880 SATED. 3572 03:06:56,880 --> 03:07:02,920 AND SO, THE VALUE OF SORT OF 3573 03:07:02,920 --> 03:07:04,080 RECAPITULATING THIS FROM EARLY 3574 03:07:04,080 --> 03:07:05,760 VISUAL CORTEX NOT BEING 3575 03:07:05,760 --> 03:07:08,800 SENSITIVE TO HUNGER IN THE WAY 3576 03:07:08,800 --> 03:07:13,000 WHICH IS KNOWN IN HUMAN SUDDEN S 3577 03:07:13,000 --> 03:07:13,760 WHAT ARE THE MECHANISMS THAT 3578 03:07:13,760 --> 03:07:15,440 MIGHT REGULATE THE PROCESSING OF 3579 03:07:15,440 --> 03:07:17,240 SPECIFIC OBJECTS IN THE WORLD 3580 03:07:17,240 --> 03:07:18,520 DEPENDING ON WHETHER WE'RE 3581 03:07:18,520 --> 03:07:25,280 HUNGRY OR THURS THIRSTY OR SATE. 3582 03:07:25,280 --> 03:07:28,000 THE VERSUS OF HUNGRY OR SATED 3583 03:07:28,000 --> 03:07:29,840 HAS A DIVERSE SET OF CHANGES IN 3584 03:07:29,840 --> 03:07:32,720 THE BODY THAT ARE ASSOCIATED. 3585 03:07:32,720 --> 03:07:34,120 AND FOR PURPOSES OF GETTING 3586 03:07:34,120 --> 03:07:39,160 STARTED WE FOCUS ON THE MEDIA 3587 03:07:39,160 --> 03:07:40,240 BASAL HYPE A THALAMUS AND THE 3588 03:07:40,240 --> 03:07:42,000 PEP TIGHT NEURONS BECAUSE IN THE 3589 03:07:42,000 --> 03:07:45,600 ASSAUSATED NEURONS IF YOU TURN N 3590 03:07:45,600 --> 03:07:47,480 THE ANIMAL WILL EAT ANOTHER 10% 3591 03:07:47,480 --> 03:07:50,200 OR MORE OF ITS BODY WEIGHT. 3592 03:07:50,200 --> 03:07:53,440 AND SO TO SUMMARIZE THE SERIES 3593 03:07:53,440 --> 03:07:56,120 OF EXPERIMENTS THIS IS A MODEL 3594 03:07:56,120 --> 03:07:57,240 WHAT WE THINK MIGHT BE 3595 03:07:57,240 --> 03:07:57,640 HAPPENING. 3596 03:07:57,640 --> 03:07:59,800 THE MOUSE SEES A PICTURE OF FOOD 3597 03:07:59,800 --> 03:08:02,720 AND THE VISUAL ASPECTS ARE 3598 03:08:02,720 --> 03:08:04,120 PROCESSED IN THE CORTEX AND 3599 03:08:04,120 --> 03:08:06,920 THALAMUS AND ROW LAID TO THE 3600 03:08:06,920 --> 03:08:11,640 AMYGDALA ONTO ON TO CORTEX. 3601 03:08:11,640 --> 03:08:14,000 THERE'S A BLOCK IN THE SATED 3602 03:08:14,000 --> 03:08:14,240 STATE. 3603 03:08:14,240 --> 03:08:15,920 WHEN THE ANIMAL IS HUNGRY AND 3604 03:08:15,920 --> 03:08:18,320 THESE AGRP NEURONS ARE ACTIVE 3605 03:08:18,320 --> 03:08:20,560 SOMEHOW IN A WAY THAT WORE STILL 3606 03:08:20,560 --> 03:08:23,400 WORKING ON, UNBLOCKS THIS 3607 03:08:23,400 --> 03:08:24,600 PATHWAY AND THE VISUAL 3608 03:08:24,600 --> 03:08:25,640 INFORMATION ABOUT FOOD IS NOW 3609 03:08:25,640 --> 03:08:28,480 GOING TO BE ABLE TO FLOW TO THE 3610 03:08:28,480 --> 03:08:29,320 INSEWALL AR CORTEX AND THAT 3611 03:08:29,320 --> 03:08:31,440 SHOULD IN TURN BE PART OF A 3612 03:08:31,440 --> 03:08:33,920 NETWORK THAT DRIVES FOOD SEEKING 3613 03:08:33,920 --> 03:08:37,080 AND ALSO AS IS SHOWN PERHAPS MY 3614 03:08:37,080 --> 03:08:48,160 PREPARE THE BODY FOR FO FO FORN 3615 03:08:50,280 --> 03:08:51,040 AND SO ON. 3616 03:08:51,040 --> 03:08:53,280 IT MIGHT UNBLOCK WATER RELATED 3617 03:08:53,280 --> 03:08:55,520 CUES IN THE INSULAR CORTEX. 3618 03:08:55,520 --> 03:08:57,760 AND FINALLY, IN A DIFFERENT SET 3619 03:08:57,760 --> 03:08:59,640 OF EXPERIMENTS IN OUR LAB, WE'VE 3620 03:08:59,640 --> 03:09:01,160 BEEN TRYING TO UNDERSTAND 3621 03:09:01,160 --> 03:09:03,120 SOMETHING ABOUT THE NATURE OF 3622 03:09:03,120 --> 03:09:05,080 CRAVINGS AND THOUGHTS REGARDING 3623 03:09:05,080 --> 03:09:07,400 FOOD AND TO TROY TO DO THIS IN A 3624 03:09:07,400 --> 03:09:08,480 MOUSE WE PRESENT THE NICE WITH 3625 03:09:08,480 --> 03:09:10,160 THESE PICTURES OF FOOD AND WE 3626 03:09:10,160 --> 03:09:12,040 TURN ON THE TV SCREEN AND RECORD 3627 03:09:12,040 --> 03:09:13,800 FROM THESE SAME NEURONS AN HOUR 3628 03:09:13,800 --> 03:09:15,360 LATER IN THE DARK AND WE CAN SEE 3629 03:09:15,360 --> 03:09:16,880 THAT THE SAME PATTERNS OF 3630 03:09:16,880 --> 03:09:20,360 NEURONS THAT WERE ACTIVATED BY 3631 03:09:20,360 --> 03:09:22,720 FOOD ARE REACTIVATED OVER AND 3632 03:09:22,720 --> 03:09:24,400 OVER OVER THE COURSE OF SEVERAL 3633 03:09:24,400 --> 03:09:25,920 HOURS AND WE THINK THAT THIS MAY 3634 03:09:25,920 --> 03:09:28,880 BE AT LEAST AN ENTRY POINT TO 3635 03:09:28,880 --> 03:09:31,840 STUDYING FOOD CRAVINGS. 3636 03:09:31,840 --> 03:09:36,000 SO, THAT WAS ABOUT FOOD CUES AND 3637 03:09:36,000 --> 03:09:37,040 WATER CUES AND WHAT ABOUT 3638 03:09:37,040 --> 03:09:38,480 REPRESENTATION OF FOOD AND WATER 3639 03:09:38,480 --> 03:09:40,720 AND HUNGER AND THIRST. 3640 03:09:40,720 --> 03:09:43,280 WE KNOW IN THE THIRSTY ANIMAL OR 3641 03:09:43,280 --> 03:09:44,880 A SATED ANIMAL, IN BOTH CASES 3642 03:09:44,880 --> 03:09:46,800 THERE'S LOTS OF NEURAL ACTIVITY 3643 03:09:46,800 --> 03:09:49,280 IN THE INSULAR CORTEX AND SOME 3644 03:09:49,280 --> 03:09:51,120 NEURONS ARE ACTIVE IN THE 3645 03:09:51,120 --> 03:09:53,080 THIRSTY STATE BUT NOT THE 3646 03:09:53,080 --> 03:09:54,000 QUENCHED STATE AND ARREST ACTIVE 3647 03:09:54,000 --> 03:09:56,960 IN THE SAME RECORDING IN THE 3648 03:09:56,960 --> 03:09:58,840 QUENCHED STATE BUT NOT THE 3649 03:09:58,840 --> 03:10:00,520 THIRSTY STATE AND IF YOU JUST 3650 03:10:00,520 --> 03:10:02,360 SUMMARIZE THIS DATA FROM 200 3651 03:10:02,360 --> 03:10:05,960 NEURONS RECORDED IN THE SAME 3652 03:10:05,960 --> 03:10:07,960 IMAGING SESSION SO YOU SEE THAT 3653 03:10:07,960 --> 03:10:09,520 SOME OF THE NEURONS IN ORIGINAL 3654 03:10:09,520 --> 03:10:11,440 ARE ACTIVE EARLY AND LESS ACTIVE 3655 03:10:11,440 --> 03:10:13,200 AS THE MOUSE BECOMES QUENCHED 3656 03:10:13,200 --> 03:10:14,760 OVER A FEW HOURS AND OTHER 3657 03:10:14,760 --> 03:10:16,440 NEURONS ARE QUIET AND THEY 3658 03:10:16,440 --> 03:10:18,720 BECOME ACTIVE IN IN OTHER WORDS, 3659 03:10:18,720 --> 03:10:21,440 THE PATTERN OF ACTIVITY ACROSS 3660 03:10:21,440 --> 03:10:22,840 THESE NEURONS IS CHANGING OVER 3661 03:10:22,840 --> 03:10:27,200 TIME AND NOT ONLY THE PEOPLE MEY 3662 03:10:27,200 --> 03:10:29,000 AND THIS IS NOT IN A MULTI 3663 03:10:29,000 --> 03:10:30,080 DIMENSIONAL SPACE WHERE EACH DOT 3664 03:10:30,080 --> 03:10:31,760 IN THE SPACE IS A PATTERN OF 3665 03:10:31,760 --> 03:10:35,800 ACTIVITIES SO THE BLUE DOTS ARY 3666 03:10:35,800 --> 03:10:38,160 PATTERNS HERE AND THE YELLOW 3667 03:10:38,160 --> 03:10:39,600 REPRESENT LATE PATTERNS OF 3668 03:10:39,600 --> 03:10:40,920 ACTIVITIES AFTER THE MOUSE 3669 03:10:40,920 --> 03:10:41,760 BECOMES QUENCHED. 3670 03:10:41,760 --> 03:10:44,120 AND WE FOUND THAT THESE CHANGES 3671 03:10:44,120 --> 03:10:45,560 IN THIS SLOW PATTERNS OF 3672 03:10:45,560 --> 03:10:46,960 ACTIVITIES OVER HOURS, REALLY I 3673 03:10:46,960 --> 03:10:48,880 THINK RELATES TO INTRA EXCEPTION 3674 03:10:48,880 --> 03:10:51,280 AND SOMEHOW AS REFLECTING THE 3675 03:10:51,280 --> 03:10:52,200 HYDRATION STATE OF THE ANIMALS 3676 03:10:52,200 --> 03:10:54,200 AND NOT CHANGES IN MOTOR 3677 03:10:54,200 --> 03:10:55,720 BEHAVIOR AS WE'VE SHOWN IN THESE 3678 03:10:55,720 --> 03:11:06,000 RECENT STUDIES. 3679 03:11:10,560 --> 03:11:12,240 WE CAN DECODE LOOKING AT THE 3680 03:11:12,240 --> 03:11:13,520 ACTIVITY THE SAME NEURONS OVER 3681 03:11:13,520 --> 03:11:17,000 DAYS SO WE THINK THAT THERE'S A 3682 03:11:17,000 --> 03:11:18,160 LOT OF INFORMATION BEYOND THESE 3683 03:11:18,160 --> 03:11:20,360 TWO DIMENSIONS IN THE SAME 3684 03:11:20,360 --> 03:11:23,080 REGION OF INSULAR CORTEX. 3685 03:11:23,080 --> 03:11:24,520 IF YOU LOCK AT THIS IN THE 3686 03:11:24,520 --> 03:11:26,840 CONTEXT OF THESE TWO DIMENSIONS, 3687 03:11:26,840 --> 03:11:30,520 HYDRATIONS AND FUEL LEVEL, YOU 3688 03:11:30,520 --> 03:11:31,960 CAN CONCEIVE OF A POINT IN THIS 3689 03:11:31,960 --> 03:11:38,960 SPACE AS JUST A STATE OF THE 3690 03:11:38,960 --> 03:11:39,200 CORTEX. 3691 03:11:39,200 --> 03:11:40,360 WHEN THE MOUSE IS HUNG ROW YOU 3692 03:11:40,360 --> 03:11:42,240 HAVE A PATTERN OF ACTIVITY 3693 03:11:42,240 --> 03:11:43,920 REFLECTED OF FOOD DEFICIT AS I 3694 03:11:43,920 --> 03:11:45,440 SAID AND WHEN THE MOUSE SEES A 3695 03:11:45,440 --> 03:11:47,080 PICTURE OF FOOD, WE FOUND WHICH 3696 03:11:47,080 --> 03:11:49,000 WAS REALLY STRIKING WAS THAT 3697 03:11:49,000 --> 03:11:50,880 ACTUALLY THIS PATTERN OF 3698 03:11:50,880 --> 03:11:52,080 ACTIVITY MOVES OVER THE COURSE 3699 03:11:52,080 --> 03:11:54,920 OF A FEW SECONDS TOWARDS THIS 3700 03:11:54,920 --> 03:11:56,480 SATED STATE THAT IS ONLY GOING 3701 03:11:56,480 --> 03:11:58,160 TO BE EXPERIENCED TWO HOURS 3702 03:11:58,160 --> 03:12:01,840 LATER AND THEN COMES BACK TO THE 3703 03:12:01,840 --> 03:12:02,920 HUNGRY STATE. 3704 03:12:02,920 --> 03:12:04,560 IS THE MOUSE IS AING WHETHER 3705 03:12:04,560 --> 03:12:06,000 SEATING A SINGLE DROP IS FOOD IS 3706 03:12:06,000 --> 03:12:07,800 GOING TO EVENTUALLY MOVE IT 3707 03:12:07,800 --> 03:12:10,960 TOWARDS THIS FUTURE SATED STATE. 3708 03:12:10,960 --> 03:12:12,960 WHEN THE MOUSE IS SATED THE 3709 03:12:12,960 --> 03:12:15,080 CORTEX BASELINE ACTIVITY 3710 03:12:15,080 --> 03:12:18,440 REFLECTS THAT SAY TEE AND WHEN 3711 03:12:18,440 --> 03:12:20,360 THE MOUSE SEES A PICTURE OF 3712 03:12:20,360 --> 03:12:21,440 FOOD, NOTHING HAPPENS BECAUSE IT 3713 03:12:21,440 --> 03:12:23,160 KNOWS THIS WON'T PUT THE FOOD IN 3714 03:12:23,160 --> 03:12:23,640 ITS MOUTH. 3715 03:12:23,640 --> 03:12:26,080 WHEN YOU TURN ON THE NEURONS 3716 03:12:26,080 --> 03:12:29,440 THAT COMPEL THE MOUSE TO PUT THE 3717 03:12:29,440 --> 03:12:31,320 FOOD IN THE MOUTH WE SEE THAT 3718 03:12:31,320 --> 03:12:34,400 NOW THIS TRIGGERS A MOVEMENT OF 3719 03:12:34,400 --> 03:12:37,120 THE INSULAR CORTEX TO THE FUTURE 3720 03:12:37,120 --> 03:12:38,960 STATE OF FOOD SURPLUS VERY MUCH 3721 03:12:38,960 --> 03:12:40,600 LIKE YOU FINISHING A HUGE MEAL 3722 03:12:40,600 --> 03:12:42,040 AND SEEING THE DESSERT TRAY 3723 03:12:42,040 --> 03:12:50,520 COMING OVER TO YOUR TABLE. 3724 03:12:50,520 --> 03:12:53,360 WE THINK THAT THE INSULAR CORTEX 3725 03:12:53,360 --> 03:12:55,000 CAN CREATE PREDICTIONS OF WHERE 3726 03:12:55,000 --> 03:12:56,800 YOU SHOULD BE AFTER LET'S SAY A 3727 03:12:56,800 --> 03:12:57,640 MEAL. 3728 03:12:57,640 --> 03:13:02,320 IF YOU ARE A PATIENT WITH AN 3729 03:13:02,320 --> 03:13:03,880 ANOREXIA AND YOU'VE EATEN 200 3730 03:13:03,880 --> 03:13:06,120 MEALS WITH 10% OF THE NEEDED 3731 03:13:06,120 --> 03:13:07,520 CALORIES THIS MAY LEAD TO A 3732 03:13:07,520 --> 03:13:08,440 PREDICTION YOU ARE GOING TO BE 3733 03:13:08,440 --> 03:13:10,800 ABLE TO STOP EATING AFTER A FEW 3734 03:13:10,800 --> 03:13:11,000 BITES. 3735 03:13:11,000 --> 03:13:14,960 AND SO, IT MAY REQUIRE 3736 03:13:14,960 --> 03:13:17,400 RECONFIGURING CORTICAL PLASTIC 3737 03:13:17,400 --> 03:13:18,960 TEE THROUGH THERAPY WHICH IS ONE 3738 03:13:18,960 --> 03:13:23,720 OF THE MOST COMMON THERAPIES FOR 3739 03:13:23,720 --> 03:13:27,360 ANOREXIA TO ANTICIPATE A MEAL 3740 03:13:27,360 --> 03:13:29,840 SETS A FULL SET OF CALORIES N 3741 03:13:29,840 --> 03:13:31,680 OBESITY IT MAY BE THE PREDICTION 3742 03:13:31,680 --> 03:13:33,120 AFTER MANY MONTHS OF OVER EATING 3743 03:13:33,120 --> 03:13:34,840 IS THAT FOOD SURPLUS SHOULD BE 3744 03:13:34,840 --> 03:13:36,840 THE END POINT OF YOUR MEAL. 3745 03:13:36,840 --> 03:13:39,800 AND THAT IT WILL REQUIRE 3746 03:13:39,800 --> 03:13:41,320 SIMILARLY PLASTICITY IN THE 3747 03:13:41,320 --> 03:13:43,840 CORTEX AND ELSEWHERE THAT WILL 3748 03:13:43,840 --> 03:13:44,760 EVENTUALLY DRIVE A CHANGE IN 3749 03:13:44,760 --> 03:13:46,880 THIS COMPASS IN THE CORTEX, A 3750 03:13:46,880 --> 03:13:48,560 CHANGE IN THE SETTLING POINT SO 3751 03:13:48,560 --> 03:13:52,400 WE CAN ACTUALLY CREATE 3752 03:13:52,400 --> 03:13:53,280 EXPECTATIONS OF WHAT A MEAL 3753 03:13:53,280 --> 03:13:55,880 SHOULD BE AND FINALLY, THERE ARE 3754 03:13:55,880 --> 03:13:57,680 DIFFERENT OTHER ACTIONS 3755 03:13:57,680 --> 03:13:59,040 REPRESENTED IN THE INSULAR 3756 03:13:59,040 --> 03:14:01,840 CORTEX IN A DISTRIBUTED MANNER 3757 03:14:01,840 --> 03:14:02,960 WITH BODY TEMPERATURE AND PAIN 3758 03:14:02,960 --> 03:14:03,800 AND SO ON. 3759 03:14:03,800 --> 03:14:05,080 HOW DO ALL THESE SIGNALS GET 3760 03:14:05,080 --> 03:14:07,800 INTO THE INSULAR CORTEX WE CAN'T 3761 03:14:07,800 --> 03:14:09,800 STUDY OR MANIPULATE THE PATTERNS 3762 03:14:09,800 --> 03:14:11,120 UNTIL WE KNOW WHERE THOSE 3763 03:14:11,120 --> 03:14:13,000 PATTERNS ARE COMING FROM AND I 3764 03:14:13,000 --> 03:14:14,800 THINK THIS IS WHERE THIS BRIDGES 3765 03:14:14,800 --> 03:14:15,760 WITH ALL THE BEAUTIFUL WORK 3766 03:14:15,760 --> 03:14:17,760 WE'VE SEEN SO FAR AND COMING 3767 03:14:17,760 --> 03:14:19,920 FROM THIS SPINAL AND VAGAL 3768 03:14:19,920 --> 03:14:21,800 INPUTS TO CONVERGENT FOR EXAMPLE 3769 03:14:21,800 --> 03:14:24,160 THE PARA NUCLEUS AND ELSEWHERE 3770 03:14:24,160 --> 03:14:26,880 AND SO THE NUCLEUS IS A REGISTER 3771 03:14:26,880 --> 03:14:29,000 ON IN THE BRAIN STEM THAT 3772 03:14:29,000 --> 03:14:31,040 RECEIVES INPUTS FROM SPINAL 3773 03:14:31,040 --> 03:14:33,920 VAGAL AND ELSEWHERE TO INTEGRATE 3774 03:14:33,920 --> 03:14:38,120 THE INTRA ACCEPTIVE STATE OF THE 3775 03:14:38,120 --> 03:14:48,680 BODY AND WITH THE INPUTS TO THE 3776 03:15:05,960 --> 03:15:06,040 TBN. 3777 03:15:06,040 --> 03:15:07,520 IF YOU LOOK AT THIS MOUSE THAT 3778 03:15:07,520 --> 03:15:09,480 IS DRINKING DROPS OF WATER YOU 3779 03:15:09,480 --> 03:15:11,000 CAN SEE OVER SEVERAL SECONDS, 3780 03:15:11,000 --> 03:15:12,280 THE DROPS OF HEAVY WATER ARE 3781 03:15:12,280 --> 03:15:14,880 MOVING THROUGH THE 3782 03:15:14,880 --> 03:15:15,720 GASTROINTESTINAL TRACK SO WE 3783 03:15:15,720 --> 03:15:17,160 THINK THAT SOMETHING IS SIMILAR 3784 03:15:17,160 --> 03:15:18,480 IS HAPPENING WHEN THE MOUSE 3785 03:15:18,480 --> 03:15:20,360 DRINKS A DROP OF MILK SHAKE YOU 3786 03:15:20,360 --> 03:15:22,000 CAN FIRST SEE A SET OF NEURONS 3787 03:15:22,000 --> 03:15:25,120 RESPONDING AT THE MOMENT THE 3788 03:15:25,120 --> 03:15:26,720 MOUSE LICKS BUT THERE ARE OTHER 3789 03:15:26,720 --> 03:15:27,920 NEURONS THAT RESPOND IN A WAVE A 3790 03:15:27,920 --> 03:15:29,760 CROSS THE LATERAL PART OF THE 3791 03:15:29,760 --> 03:15:31,960 NUKELY US AND SOME OF THEM ARE 3792 03:15:31,960 --> 03:15:32,880 RESPONDING FIVE SECONDS AFTER 3793 03:15:32,880 --> 03:15:35,600 THE MOUSE HAS INGESTED THE MILK 3794 03:15:35,600 --> 03:15:36,800 SHAKE SUGGESTING THAT THERE 3795 03:15:36,800 --> 03:15:38,080 MAYBE NEURONS IN CODING EACH 3796 03:15:38,080 --> 03:15:41,640 PART OF THE G.I. TRACT. 3797 03:15:41,640 --> 03:15:42,640 AT THE SAME TIME, WE CAN 3798 03:15:42,640 --> 03:15:48,640 INTERETRACK MILDTAIL SHOCKS ANDO 3799 03:15:48,640 --> 03:15:50,600 STIMULATION OF FEEDBACK FROM THE 3800 03:15:50,600 --> 03:15:53,920 INSULAR CORTEX BACK TO THE PBM 3801 03:15:53,920 --> 03:15:55,600 WHICH IS STRONG AND DRIVES 3802 03:15:55,600 --> 03:15:59,600 PATRONS RESPONSE AND WE THINK 3803 03:15:59,600 --> 03:16:02,360 MIGHT BE IMPORTANT FOR IN EXTRA 3804 03:16:02,360 --> 03:16:03,480 ACCEPTIVE STATES WHEN THEY'RE 3805 03:16:03,480 --> 03:16:03,800 NOT HAM. 3806 03:16:03,800 --> 03:16:10,640 SO IF YOU WANT THE HYPOTHALIMUS 3807 03:16:10,640 --> 03:16:12,200 AND THE BRAIN STEAM MAY ALLOW 3808 03:16:12,200 --> 03:16:16,000 THE BRAIN TO LON HOW TO BEST 3809 03:16:16,000 --> 03:16:19,440 ANTICIPATE KEEFEATIONS FROM HOME 3810 03:16:19,440 --> 03:16:20,160 YO STAY ADVERTISE AND TO 3811 03:16:20,160 --> 03:16:22,160 STIMULATE HOW THE BODY FEELS ON 3812 03:16:22,160 --> 03:16:27,120 UPCOMING ACTIONS AND ADAPT 3813 03:16:27,120 --> 03:16:27,840 DECISION MAKING AND TO MAKE 3814 03:16:27,840 --> 03:16:29,320 PROGRESS IN TRYING TO UNDERSTAND 3815 03:16:29,320 --> 03:16:32,080 THESE CENTRAL CIRCUITS, INVOLVED 3816 03:16:32,080 --> 03:16:34,960 IN INTRA DECISION MUCH HAS BEEN 3817 03:16:34,960 --> 03:16:37,200 THE CASE IN OTHER SENSORY 3818 03:16:37,200 --> 03:16:38,280 SYSTEMS LIKE VISION WHERE THE 3819 03:16:38,280 --> 03:16:40,080 KNOWLEDGE OF GENETIC CELL TYPES 3820 03:16:40,080 --> 03:16:45,840 IN THE RETINA HAVE MADE HUGE 3821 03:16:45,840 --> 03:16:47,160 CONTRIBUTION TO OUR ABILITY TO 3822 03:16:47,160 --> 03:16:48,560 UNDERSTAND CENTRAL CIRCUITS FOR 3823 03:16:48,560 --> 03:16:50,680 VISION AND IT'S GOING TO BE 3824 03:16:50,680 --> 03:16:51,680 CRITICAL TO FORGE COLLABORATIONS 3825 03:16:51,680 --> 03:16:56,080 AND MANY OF THE LABS HERE IN 3826 03:16:56,080 --> 03:16:59,080 ELSEWHERE THAT STUDY IT MORE 3827 03:16:59,080 --> 03:17:01,720 PERIPHERALLY AND USE THESE 3828 03:17:01,720 --> 03:17:02,560 ENTRIES POINTS TO BETTER 3829 03:17:02,560 --> 03:17:03,400 UNDERSTAND CENTRAL PROCESSING 3830 03:17:03,400 --> 03:17:08,520 AND WITH THAT, I WANT TO THANK 3831 03:17:08,520 --> 03:17:10,040 OUR MEMBERS OF THE LAB PAST AND 3832 03:17:10,040 --> 03:17:13,200 PRESENT WHO ARE PUSHING HARD 3833 03:17:13,200 --> 03:17:15,200 TOWARDS THIS GOAL AND OUR 3834 03:17:15,200 --> 03:17:16,080 COLLABORATORS AND A BIG THANK 3835 03:17:16,080 --> 03:17:18,480 YOU AT THE NCCIH AND TO OTHER 3836 03:17:18,480 --> 03:17:20,440 SOURCES OF FUNDING AND THANK YOU 3837 03:17:20,440 --> 03:17:24,280 VERY MUCH FOR YOUR ATTENTION. 3838 03:17:24,280 --> 03:17:27,960 PLOWS. 3839 03:17:27,960 --> 03:17:32,840 >>WE COULD TAKE ONE QUESTION IF 3840 03:17:32,840 --> 03:17:33,440 THERE'S ONE. 3841 03:17:33,440 --> 03:17:35,240 IF NOT I CAN TAKE THE 3842 03:17:35,240 --> 03:17:38,160 OPPORTUNITY TO ASK A QUESTION 3843 03:17:38,160 --> 03:17:38,560 QI. 3844 03:17:38,560 --> 03:17:39,600 YOU START TODAY GET TO THIS 3845 03:17:39,600 --> 03:17:41,720 TOWARDS THE END OF YOUR TALK AND 3846 03:17:41,720 --> 03:17:42,560 REALLY HONING IN ON THE OTHER 3847 03:17:42,560 --> 03:17:44,360 SOURCE OF INPUTS AND ONE OF 3848 03:17:44,360 --> 03:17:53,320 WHICH IS CARDIAC AND DUNG HUNGER 3849 03:17:53,320 --> 03:17:55,040 AND SATE, HOW WOULD YOU INDICATE 3850 03:17:55,040 --> 03:17:56,680 THAT INTO THE WORKING PARADIGM 3851 03:17:56,680 --> 03:17:56,960 YOU HAVE? 3852 03:17:56,960 --> 03:17:59,680 >>OUR HOPE IS TO BASICALLY BE 3853 03:17:59,680 --> 03:18:02,160 ABLE TO TRACK DIFFERENT 3854 03:18:02,160 --> 03:18:03,080 PHYSIOLOGICAL STATES WITH AND 3855 03:18:03,080 --> 03:18:05,680 WITHOUT SILENCING OF VARIOUS 3856 03:18:05,680 --> 03:18:16,200 LET'S SAY SPINAL AND DO THIS IN 3857 03:18:17,160 --> 03:18:19,200 A SUBTLE WAY SO WE DON'T KIND OF 3858 03:18:19,200 --> 03:18:20,160 FREAK OUT THE ANIMAL WHICH I 3859 03:18:20,160 --> 03:18:22,400 THINK IS A CONFOUND IN A LOT OF 3860 03:18:22,400 --> 03:18:23,680 THESE STUDIES TRYING TO 3861 03:18:23,680 --> 03:18:25,000 UNDERSTAND AND OVER ALL STATE 3862 03:18:25,000 --> 03:18:34,040 AND WHAT IS CON TRIB TO USE THE. 3863 03:18:34,040 --> 03:18:37,480 >>I WOULD LIKE TO THANK NIH 3864 03:18:37,480 --> 03:18:38,440 STAFF FOR ORGANIZING THIS 3865 03:18:38,440 --> 03:18:40,920 MEETING AND THE OPPORTUNITY TO 3866 03:18:40,920 --> 03:18:46,360 PRESENT AND MY LAB IS INTERESTED 3867 03:18:46,360 --> 03:18:49,120 IN THE INTEROCEPTIVE FORM OF 3868 03:18:49,120 --> 03:18:51,000 LEPTIN THAT IS PRODUCED AND 3869 03:18:51,000 --> 03:18:53,200 RELEASED FROM ADDIE POSE TISSUE 3870 03:18:53,200 --> 03:18:54,840 IN A CIRCULATION WHICH IT 3871 03:18:54,840 --> 03:19:00,440 REACHES THE BRAIN THE HYPE A 3872 03:19:00,440 --> 03:19:07,640 THALAMUS AND AND IT REGULATES 3873 03:19:07,640 --> 03:19:10,480 BODY TISSUE AND LEPTIN LEVELS 3874 03:19:10,480 --> 03:19:13,960 ARE HIGHLY RESPONSES TO CHANGES 3875 03:19:13,960 --> 03:19:16,080 IN FOR EXAMPLE EX TER OWE 3876 03:19:16,080 --> 03:19:17,320 EXCEPTION AND AS WELL AS TO 3877 03:19:17,320 --> 03:19:18,760 ENERGY STATES LIKE FASTING OR 3878 03:19:18,760 --> 03:19:20,760 OVER FEEDING. 3879 03:19:20,760 --> 03:19:25,720 AND LEPTIN OVER ALL IS NO ONE TO 3880 03:19:25,720 --> 03:19:28,800 ACT ON FUNCTIONS AND IT'S ALSO 3881 03:19:28,800 --> 03:19:30,120 ASSOCIATED WITH A BUNCH OF 3882 03:19:30,120 --> 03:19:32,840 DISEASES AND ILLNESSES AND WHERE 3883 03:19:32,840 --> 03:19:36,440 PARTICULARLY WE'RE INTERESTED IN 3884 03:19:36,440 --> 03:19:37,720 OBESITY AND DIABETES. 3885 03:19:37,720 --> 03:19:40,240 WE ARE INTERESTED ALSO IN THE 3886 03:19:40,240 --> 03:19:44,280 ROLE OF LEPTIN AND ENERGY 3887 03:19:44,280 --> 03:19:49,200 EXPENDITURE AND FOR FOOD TAKE 3888 03:19:49,200 --> 03:19:51,680 AND OVER ALL PEOPLE ASSUME THAT 3889 03:19:51,680 --> 03:19:54,480 LEPTIN INCREASES ENERGY 3890 03:19:54,480 --> 03:19:55,640 EXPENDITURE BUT IT SHOES IT'S 3891 03:19:55,640 --> 03:19:58,800 NOT EXACTLY TRUE IF YOU MEASURE 3892 03:19:58,800 --> 03:20:00,480 METABOLIC RATE AND INJECT LEPTIN 3893 03:20:00,480 --> 03:20:02,000 IN FAT ANIMALS THERE'S NO EFFECT 3894 03:20:02,000 --> 03:20:09,120 ON ENERGY EXPENDITURE 3895 03:20:09,120 --> 03:20:19,320 WHATSOEVER. 3896 03:20:21,920 --> 03:20:25,440 FASTING AND FOOD RESTRICTION 3897 03:20:25,440 --> 03:20:27,520 CAUSE A AND IT'S HYPO METABOLIC 3898 03:20:27,520 --> 03:20:31,600 STATE AND THAT'S ALSO TRUE IN 3899 03:20:31,600 --> 03:20:35,720 HUMANS AND VERY DIFFERENT 3900 03:20:35,720 --> 03:20:39,160 SITUATION IS AMY AN TEMPERATURE 3901 03:20:39,160 --> 03:20:40,240 AND FOR LEPTIN DEFICIENT MICE 3902 03:20:40,240 --> 03:20:41,520 THEY HAVE A DECREASE BODY 3903 03:20:41,520 --> 03:20:43,040 TEMPERATURE AND IF YOU EXPOS 3904 03:20:43,040 --> 03:20:44,880 THEM TO COLD THEY ARE UNABLE TO 3905 03:20:44,880 --> 03:20:48,480 MAINTAIN THEIR BODY TEMPERATURE 3906 03:20:48,480 --> 03:20:49,560 EVEN THOUGH THEY HAVE NO 3907 03:20:49,560 --> 03:20:53,880 PROBLEMS TO DO THAT AND THAT IS 3908 03:20:53,880 --> 03:20:55,720 CURIOUS BECAUSE IT DECREASED 3909 03:20:55,720 --> 03:20:58,520 LEPTIN LEVELS EVEN MORE DRAMATIC 3910 03:20:58,520 --> 03:20:59,560 THAN FASTING AND IN A WAY THEY 3911 03:20:59,560 --> 03:21:01,280 HAVE THE SAME LOW LEPTIN LEVELS 3912 03:21:01,280 --> 03:21:03,840 BUT THEY RESPOND VERY 3913 03:21:03,840 --> 03:21:04,920 DIFFERENTLY THAT WE DON'T REALLY 3914 03:21:04,920 --> 03:21:15,240 UNDERSTAND NOWADAYS. 3915 03:21:34,320 --> 03:21:36,760 AND ALSO MET WITH LEPTIN LEVELS 3916 03:21:36,760 --> 03:21:40,400 UNKNOWN TO BE IMPORTANT FOR 3917 03:21:40,400 --> 03:21:45,640 ADIPOSE TISSUE INNERRIZATION AND 3918 03:21:45,640 --> 03:21:50,520 LEPTIN CAN RECOVER THAT. 3919 03:21:50,520 --> 03:21:54,280 TO START TO UNDERSTAND THESE 3920 03:21:54,280 --> 03:21:56,520 ASSOCIATIONS, WE INITIALLY 3921 03:21:56,520 --> 03:22:00,120 IDENTIFIED LEPTIN RECEPTORS IN 3922 03:22:00,120 --> 03:22:03,200 THE BRAIN AND THE REOPTIC AREA 3923 03:22:03,200 --> 03:22:04,640 THAT MODULATE ENERGY EXPENDITURE 3924 03:22:04,640 --> 03:22:06,920 AND THESE IS PART OF A 3925 03:22:06,920 --> 03:22:12,600 REGULATORY CIRCUIT THAT 3926 03:22:12,600 --> 03:22:15,200 INNOVATION TO BROWN ADIPOSE 3927 03:22:15,200 --> 03:22:18,240 TISSUE AND IF WE CAN STIMULATE 3928 03:22:18,240 --> 03:22:20,760 WE INCREASE ENERGY EXPENDITURE 3929 03:22:20,760 --> 03:22:22,960 SIMILAR TO CODE EXPOSURE AND IF 3930 03:22:22,960 --> 03:22:26,240 WE STIMULATE PRO OPTIC AREA 3931 03:22:26,240 --> 03:22:28,360 NEURONS WE DECREASE ENERGY 3932 03:22:28,360 --> 03:22:30,280 EXPENDITURE SIMILAR TO WARM 3933 03:22:30,280 --> 03:22:32,040 EXPOSURE OR FASTING. 3934 03:22:32,040 --> 03:22:35,240 AND WE ALSO WANTED TO TEST IF 3935 03:22:35,240 --> 03:22:39,960 THIS IS REALLY BY SYMPATHETIC 3936 03:22:39,960 --> 03:22:43,160 ADIPOSE TISSUE AND WE USE THE 3937 03:22:43,160 --> 03:22:44,720 BATTLE 3 TO BLOCK THE EFFECT AND 3938 03:22:44,720 --> 03:22:47,640 TO SEE HERE THAT WE CAN 3939 03:22:47,640 --> 03:22:48,680 SUCCESSFULLY SUPPRESSION THE 3940 03:22:48,680 --> 03:22:50,600 INDUCTION OF ENERGY EXPENDITURE 3941 03:22:50,600 --> 03:22:52,800 WITH A ANTAGONIST BUT YOU CAN 3942 03:22:52,800 --> 03:22:53,920 ALSO APPRECIATE WITH STILL 3943 03:22:53,920 --> 03:22:55,600 MAINTAIN A GOOD A LOT OF THE 3944 03:22:55,600 --> 03:22:56,040 RESPONSE. 3945 03:22:56,040 --> 03:22:58,000 AND SIMILARLY HERE, WE TRIED TO 3946 03:22:58,000 --> 03:23:02,280 BLOCK THE SUPPRESSION OF ENERGY 3947 03:23:02,280 --> 03:23:06,160 EXPENDITURE WITH AGONIST AND WE 3948 03:23:06,160 --> 03:23:08,680 DO IT AND WE STILL HAVE A 3949 03:23:08,680 --> 03:23:09,880 SIGNIFICANT SUPPRESSION OF 3950 03:23:09,880 --> 03:23:12,320 ENERGY EXPENDITURE AND WHAT THAT 3951 03:23:12,320 --> 03:23:15,240 SAYS IS THAT THREE ALONE CANNOT 3952 03:23:15,240 --> 03:23:16,720 FULLY EXPLAIN THE EFFECT ON 3953 03:23:16,720 --> 03:23:19,400 ENERGY EXPENDITURES AND ALSO IT 3954 03:23:19,400 --> 03:23:21,360 DOESN'T REALLY TELL US IF BROWN 3955 03:23:21,360 --> 03:23:23,800 FAT ACTIVATION ALONE IS 3956 03:23:23,800 --> 03:23:26,080 SUFFICIENT FOR THE ENERGY 3957 03:23:26,080 --> 03:23:27,640 EXPENDITURE ADAPTATION WHICH IS 3958 03:23:27,640 --> 03:23:32,560 THE DARK MAGIC SO IN 1997, BRAD 3959 03:23:32,560 --> 03:23:37,280 LILLY'S GROUP HAD DATA ON THAT 3960 03:23:37,280 --> 03:23:38,680 SO HERE THEY HAVE WHOLE BODY 3961 03:23:38,680 --> 03:23:41,160 KNOCK OUT ANIMALS AND THAT FULLY 3962 03:23:41,160 --> 03:23:44,840 SUPPRESSED THE EFFECT OF CL BY 3963 03:23:44,840 --> 03:23:46,480 THE THREE AGO NISTS TO INCREASE 3964 03:23:46,480 --> 03:23:48,880 ENERGY EXPENDITURES AND THEN 3965 03:23:48,880 --> 03:23:51,720 THEY REEXPRESSED BETTER 3 3966 03:23:51,720 --> 03:23:53,400 RECEPTORS AND BROWN AND THAT IS 3967 03:23:53,400 --> 03:23:57,040 NOT ABLE TO RECOVER THE EFFECT 3968 03:23:57,040 --> 03:23:59,640 ON ENERGY EXPENDITURE HOWEVER, 3969 03:23:59,640 --> 03:24:02,120 THE BROWN AND WHITE FULLY COULD 3970 03:24:02,120 --> 03:24:04,440 RECOVER THIS EFFECT. 3971 03:24:04,440 --> 03:24:05,680 ALREADY HINTING THAT YOU MAY 3972 03:24:05,680 --> 03:24:07,640 NEED BOTH SYMPATHETIC BROWN AND 3973 03:24:07,640 --> 03:24:09,640 WHITE FOR ACTIVATION. 3974 03:24:09,640 --> 03:24:11,640 NOW MORE RECENTLY, IT HAS BEEN 3975 03:24:11,640 --> 03:24:15,200 SHOWN THAT BLOCKING GENES IN 3976 03:24:15,200 --> 03:24:16,960 BROWN AND ALSO NOT ESSENTIAL FOR 3977 03:24:16,960 --> 03:24:20,400 CODE INDUCED AND AGAIN 3978 03:24:20,400 --> 03:24:21,920 QUESTIONING THE DOGMATIC VIEW WE 3979 03:24:21,920 --> 03:24:26,640 HAVE NOWADAYS THAT BROWN 3980 03:24:26,640 --> 03:24:28,000 ACTIVATIONS FROM ITSELF IS ABLE 3981 03:24:28,000 --> 03:24:29,880 TO DRIVE ENERGY EXPENDITURE SO 3982 03:24:29,880 --> 03:24:32,840 WE WANTED TO IDENTIFY IF 3983 03:24:32,840 --> 03:24:35,600 ISOLATED SYMPATHETIC ACTIVATION 3984 03:24:35,600 --> 03:24:38,880 IS THAT SUFFICIENT FOR SOME 3985 03:24:38,880 --> 03:24:42,240 AGENDA AND LEPTIN AND TO 3986 03:24:42,240 --> 03:24:42,880 SUPPRESSION LEPTIN EXPRESSION. 3987 03:24:42,880 --> 03:24:47,120 TO DO THAT WE NEEDED TO TARGET 3988 03:24:47,120 --> 03:24:53,000 SELECTIVELY IBAT AND WE USED AN 3989 03:24:53,000 --> 03:24:55,480 RETROGRADE INJECT NOD BROWN 3990 03:24:55,480 --> 03:24:58,360 ADIPOSE TISSUE AND WITH A REPORT 3991 03:24:58,360 --> 03:25:01,680 AMOUNTS ARE LINE WE CAN NICELY 3992 03:25:01,680 --> 03:25:04,040 SEE THE SYMPATHETIC NEURONS THAT 3993 03:25:04,040 --> 03:25:07,120 ARE BROWN FED ELATED AND THE 3994 03:25:07,120 --> 03:25:08,560 DISTRIBUTION OF THOSE FROM 3995 03:25:08,560 --> 03:25:10,720 CELLULAR TO T5 WHICH IS 3996 03:25:10,720 --> 03:25:12,400 CONSISTENT TO WHAT WE HAD 3997 03:25:12,400 --> 03:25:18,280 PUBLISHED BEFORE USING WE CAN 3998 03:25:18,280 --> 03:25:19,480 ALSO COUNT THESE CELLS AND WE 3999 03:25:19,480 --> 03:25:21,960 GET A FAIR AMOUNT OF NEURONS IN 4000 03:25:21,960 --> 03:25:23,880 EACH GANGLION AND WE ALSO CAN 4001 03:25:23,880 --> 03:25:27,000 LOOK AT SENSORY NEURONS SO EVEN 4002 03:25:27,000 --> 03:25:29,240 THOUGH WE GET FAR LESS SENSORY 4003 03:25:29,240 --> 03:25:31,400 NEURONS WE HAVE A SMALL AND 4004 03:25:31,400 --> 03:25:32,800 CONSISTENT NUMBER OF SENSORY 4005 03:25:32,800 --> 03:25:35,280 NEURONS THAT WE TARGET AS WELL. 4006 03:25:35,280 --> 03:25:41,920 AND NEXT, WE USE THE MOUSE LINE 4007 03:25:41,920 --> 03:25:44,640 TO BE ABLE TO SPECIFICALLY 4008 03:25:44,640 --> 03:25:47,880 ACTIVATE THESE NEURONS. 4009 03:25:47,880 --> 03:25:49,880 NOW, IT'S COMMON IN THE CENTRAL 4010 03:25:49,880 --> 03:25:51,760 NERVOUS SYSTEM AND WE USE THE 4011 03:25:51,760 --> 03:25:53,560 GOLD STANDARD TO VERIFY OUR 4012 03:25:53,560 --> 03:25:56,080 SYSTEM OVER ALL WORKS AND WE USE 4013 03:25:56,080 --> 03:26:00,240 RECORDING IN COLLABORATION WITH 4014 03:26:00,240 --> 03:26:05,240 OUR INSTITUTE SO WE ATTACH ON TO 4015 03:26:05,240 --> 03:26:08,480 THESE GREEN NEURONS AND YOU ARE 4016 03:26:08,480 --> 03:26:11,360 CERTIFY THE IS ABLE TO CHANGE 4017 03:26:11,360 --> 03:26:14,560 THE MEMBRANE POTENTIAL IN OUR 4018 03:26:14,560 --> 03:26:16,080 BROWN FAT SYMPATHETIC AND YOU 4019 03:26:16,080 --> 03:26:19,080 CAN SEE THE VAST MAJORITY OF 4020 03:26:19,080 --> 03:26:22,960 THOSE NEURONS RESPOND VERY 4021 03:26:22,960 --> 03:26:33,160 ROBUSTLY. 4022 03:26:51,040 --> 03:26:52,880 CONFIRMING THE SET UP WORKS VERY 4023 03:26:52,880 --> 03:26:53,080 WELL. 4024 03:26:53,080 --> 03:26:56,080 IF WE LOOK IN VIVO AND ACUTE 4025 03:26:56,080 --> 03:26:59,720 ANESTHESIAIA MOUSE MODEL, WE 4026 03:26:59,720 --> 03:27:00,520 RECORD BROWN TEMPERATURE HERE 4027 03:27:00,520 --> 03:27:04,200 AND INITIALLY WE USE VERIFY TO 4028 03:27:04,200 --> 03:27:07,640 WE CAN SEE INCREASED TEMPERATURE 4029 03:27:07,640 --> 03:27:10,480 AND YOU SEE HERE A NICE INCREASE 4030 03:27:10,480 --> 03:27:13,880 IN TEMPERATURE AND HOWEVER IT 4031 03:27:13,880 --> 03:27:15,040 WOULD STIMULATE SYMPATHETICS WE 4032 03:27:15,040 --> 03:27:19,360 DON'T GET AN EFFECT ON THE 4033 03:27:19,360 --> 03:27:21,040 TEMPERATURE TO THE CONTRARY WE 4034 03:27:21,040 --> 03:27:23,320 SEE IN THE SECOND FACE AFTER 30 4035 03:27:23,320 --> 03:27:28,200 MINUTES IT DECREASE IN BROWN FAT 4036 03:27:28,200 --> 03:27:29,720 TEMPERATURE AND TO VERY FINE 4037 03:27:29,720 --> 03:27:32,320 MAYBE WE DO NEED MORE COMPLEX 4038 03:27:32,320 --> 03:27:34,360 SYMPATHETIC STIMULATION MAYBE OF 4039 03:27:34,360 --> 03:27:36,240 WHITE AND BROWN ADIPOSE TISSUE 4040 03:27:36,240 --> 03:27:38,600 AND WE USED ANOTHER MOUSE MODEL 4041 03:27:38,600 --> 03:27:43,080 WHERE WE HAVE TH CREED DRIVING 4042 03:27:43,080 --> 03:27:44,360 RECEPTORS EXPRESSION SO HERE WE 4043 03:27:44,360 --> 03:27:46,560 CAN STIMULATE ALL THE 4044 03:27:46,560 --> 03:27:47,840 SYMPATHETIC NEURONS AND IN DEED 4045 03:27:47,840 --> 03:27:49,600 IN THIS MOUSE MODEL WE SEE 4046 03:27:49,600 --> 03:27:51,520 NICELY AN INCREASE IN BROWN FAT 4047 03:27:51,520 --> 03:27:52,840 TEMPERATURE BUT STILL WE 4048 03:27:52,840 --> 03:27:54,960 MAINTAIN IN THE SECOND PHASE THE 4049 03:27:54,960 --> 03:27:57,280 SUPPRESS I HAVE EFFECT ON BROWN 4050 03:27:57,280 --> 03:27:59,800 FAT TEMPERATURE AND HERE IN THE 4051 03:27:59,800 --> 03:28:03,000 FOURTH MOUSE MODEL, WE COMBINE 4052 03:28:03,000 --> 03:28:06,440 TL INJECTIONS WITH OUR 4053 03:28:06,440 --> 03:28:08,920 SYMPATHETIC IBAT STIMULATION AND 4054 03:28:08,920 --> 03:28:10,560 WE MAINTAIN THE INCREASE IN 4055 03:28:10,560 --> 03:28:12,960 TEMPERATURE HERE BUT THEN AGAIN 4056 03:28:12,960 --> 03:28:14,240 INHIBITORY EFFECT AND WE CAN 4057 03:28:14,240 --> 03:28:16,240 ALSO DO THAT IN FRO MOVING 4058 03:28:16,240 --> 03:28:19,800 ANIMALS USING A MILLIMETER 4059 03:28:19,800 --> 03:28:20,840 SYSTEM TO MEASURE CORE 4060 03:28:20,840 --> 03:28:22,880 TEMPERATURE AND CL INCREASES 4061 03:28:22,880 --> 03:28:24,320 CORE TEMPERATURE AND THEN THE 4062 03:28:24,320 --> 03:28:30,080 COMBINED EFFECT OF CL AND CNO 4063 03:28:30,080 --> 03:28:31,160 INITIALLY IS SUPPRESSING THE 4064 03:28:31,160 --> 03:28:33,640 EFFECT OF CL HOWEVER INTERESTING 4065 03:28:33,640 --> 03:28:34,800 SURPRISINGLY IN THE LONG-TERM, 4066 03:28:34,800 --> 03:28:38,000 WE ACTUALLY FEEL SYNERGISTIC 4067 03:28:38,000 --> 03:28:39,680 EFFECT WHERE BROWN FAT CORE 4068 03:28:39,680 --> 03:28:42,200 TEMPERATURE STAYS ELEVATED 4069 03:28:42,200 --> 03:28:45,400 COMPARED TO CL ALONE AND IN DEED 4070 03:28:45,400 --> 03:28:49,440 WE ALSO NOTICED THAT AFTER 24 4071 03:28:49,440 --> 03:28:50,720 HOURS, IT WAS SUPPRESSED WHICH 4072 03:28:50,720 --> 03:28:53,400 IS NOT OBSERVED AND THE 4073 03:28:53,400 --> 03:29:00,520 INDIVIDUAL INJECTION AND THE 4074 03:29:00,520 --> 03:29:10,680 DIRECT. 4075 03:29:11,560 --> 03:29:16,520 WE SEE HERE BETTER SIGNALING 4076 03:29:16,520 --> 03:29:19,480 AGAINST ARE VASTLY INTENSE IN 4077 03:29:19,480 --> 03:29:21,200 THIS CO EXPRESSION STIMULATION 4078 03:29:21,200 --> 03:29:24,880 OF CL AND BRONZE FAT 4079 03:29:24,880 --> 03:29:27,360 SYMPATHETICS THAT WE DO NOT SEE 4080 03:29:27,360 --> 03:29:29,840 IN THE INDIVIDUAL STIMULATIONS 4081 03:29:29,840 --> 03:29:32,120 AND IF YOU LOOK AT GENES THAT 4082 03:29:32,120 --> 03:29:34,840 ARE UP REGULATED BY BROWN FAT 4083 03:29:34,840 --> 03:29:36,240 SYMPATHETIC ALONE THIS IS FROM 4084 03:29:36,240 --> 03:29:38,200 THE COMPLIMENT IN IMMUNE SYSTEM 4085 03:29:38,200 --> 03:29:44,560 IT SEEMS TO BE INVOLVED SO WE 4086 03:29:44,560 --> 03:29:46,840 LOOKED AT LEPTIN EXPRESSION AND 4087 03:29:46,840 --> 03:29:49,520 BRONZE SYMPATHETICS TO NOT 4088 03:29:49,520 --> 03:29:50,600 SUPPRESSION LEPTIN LEVELS AND TO 4089 03:29:50,600 --> 03:29:54,160 THE CONTRARY THEY SEEM TO 4090 03:29:54,160 --> 03:29:55,880 INCREASE IT BUT THEY DO NOT 4091 03:29:55,880 --> 03:29:57,800 PREVENT THE SUPPRESSION OF 4092 03:29:57,800 --> 03:30:00,800 LEPTIN BY BETTER THREE ADD INOID 4093 03:30:00,800 --> 03:30:02,000 STIMULATION AND INTERESTINGLY WE 4094 03:30:02,000 --> 03:30:05,440 ALSO SEE SOME OTHER 4095 03:30:05,440 --> 03:30:06,640 INTEROCEPTIVE SIGNALS THAT ARE 4096 03:30:06,640 --> 03:30:08,200 ENHANCED WITH THE COMBINED 4097 03:30:08,200 --> 03:30:10,960 EFFECT AND SEEM TO BE AND COULD 4098 03:30:10,960 --> 03:30:13,120 BE INVOLVED IN THE EFFECT ON 4099 03:30:13,120 --> 03:30:14,080 BODY WEIGHT. 4100 03:30:14,080 --> 03:30:16,880 SO IN SUMMARY, SYMPATHETIC 4101 03:30:16,880 --> 03:30:18,920 ACTIVATION IN ISOLATES MAY BE 4102 03:30:18,920 --> 03:30:21,520 NECESSARY FOR SOME BUT IT'S NOT 4103 03:30:21,520 --> 03:30:24,840 SUFFICIENT TO INDUCE SOME ALONE. 4104 03:30:24,840 --> 03:30:28,560 AND SYMPATHETIC IBAT ACTIVATION 4105 03:30:28,560 --> 03:30:30,960 COUNTER SIGNALING IN THE SHORT 4106 03:30:30,960 --> 03:30:32,720 TERM BUT LONG-TERM, IT ENHANCES 4107 03:30:32,720 --> 03:30:35,080 ALPHA AND BETA SIGNALING AND 4108 03:30:35,080 --> 03:30:38,120 WEIGHT LOSS. 4109 03:30:38,120 --> 03:30:41,040 AND LEPTIN mRNA EXPRESSION IS 4110 03:30:41,040 --> 03:30:42,520 SUPPRESSED BY THROW ACCUMULATION 4111 03:30:42,520 --> 03:30:47,360 BUT WAS INCREASED BY ISOLATED 4112 03:30:47,360 --> 03:30:47,720 IBAT ACTIVATION. 4113 03:30:47,720 --> 03:30:49,200 AND SO LAST BUT NOT LEAST I 4114 03:30:49,200 --> 03:30:52,840 WOULD LIKE TO THANK FORMER AND 4115 03:30:52,840 --> 03:30:56,800 CURRENT LAB MEMBERS AS WELL AS 4116 03:30:56,800 --> 03:30:57,120 COLLABORATORS. 4117 03:30:57,120 --> 03:30:59,440 AND I WOULD ALSO LIKE TO THANK 4118 03:30:59,440 --> 03:31:01,080 NIH FOR THE FUNDING OVER THE 4119 03:31:01,080 --> 03:31:04,360 YEARS AND SPECIFICALLY FOR THIS 4120 03:31:04,360 --> 03:31:08,960 PROJECT FOR NIH BLUE PRINT AND 4121 03:31:08,960 --> 03:31:09,280 INTEROCEPTION. 4122 03:31:09,280 --> 03:31:09,560 THANK YOU. 4123 03:31:09,560 --> 03:31:14,080 [Please stan [APPLAUSE] 4124 03:31:14,080 --> 03:31:20,720 >>THANK YOU, THA ANY QUESTIONS? 4125 03:31:20,720 --> 03:31:21,840 MAYBE IN THE INTEREST OF TIME WE 4126 03:31:21,840 --> 03:31:23,800 CAN MOVE ON AND THEN WE'LL TAKE 4127 03:31:23,800 --> 03:31:24,840 QUESTIONS FROM THE AUDIENCE IN 4128 03:31:24,840 --> 03:31:35,160 THE Q&A, THANK YOU. 4129 03:31:40,760 --> 03:31:42,520 >>HI, EVERYONE, THANK YOU FOR 4130 03:31:42,520 --> 03:31:44,640 ORGANIZING THIS NICE MEETING AND 4131 03:31:44,640 --> 03:31:46,040 IT'S A GREAT PLEASURE AND I 4132 03:31:46,040 --> 03:31:48,040 WANTED TO TALK ABOUT MY RESEARCH 4133 03:31:48,040 --> 03:31:49,720 HERE AT NIH INTEROCEPTION. 4134 03:31:49,720 --> 03:31:52,320 TODAY, I'M GOING TO TALK ABOUT 4135 03:31:52,320 --> 03:31:55,880 THIS FUNCTIONAL FUNCTIONAL 4136 03:31:55,880 --> 03:31:57,200 PERIPHERAL AND CENTRAL VAGAL 4137 03:31:57,200 --> 03:32:00,000 NEURAL CIRCUITS OF INTRO 4138 03:32:00,000 --> 03:32:01,360 EXCEPTION INHIBITING PAIN. 4139 03:32:01,360 --> 03:32:03,360 IT'S DIFFERENT THAN THE PHYSICAL 4140 03:32:03,360 --> 03:32:13,600 OLE TEE IN THE ORGAN. 4141 03:32:13,600 --> 03:32:18,520 SO VAGAL INTRO EXCEPTION IS 4142 03:32:18,520 --> 03:32:21,000 INTERSECTION WITH PATHWAYS TO 4143 03:32:21,000 --> 03:32:24,640 PAIN FROM TEMPORAL JOINTS WHICH 4144 03:32:24,640 --> 03:32:28,280 IS SECOND TO JOINT IN OUR BODY. 4145 03:32:28,280 --> 03:32:28,480 HERE. 4146 03:32:28,480 --> 03:32:31,880 SO IN ONE, WE WILL WILL 4147 03:32:31,880 --> 03:32:40,880 DELINEATE VAGAL THAT MEDIATES -- 4148 03:32:40,880 --> 03:32:45,800 IT'S DEFINABLE VAGAL AND MEDIATE 4149 03:32:45,800 --> 03:32:48,600 THE PAIN FROM TMJ INFLAMMATION 4150 03:32:48,600 --> 03:32:51,240 SO WE WILL DETERMINE VAGAL 4151 03:32:51,240 --> 03:32:58,440 STIMULATION IN THIS AND TMJ PAIN 4152 03:32:58,440 --> 03:33:00,880 BY OVERLAYING SUBSET AND OUR 4153 03:33:00,880 --> 03:33:05,160 ACTIVATION USING THE ACTIVATION. 4154 03:33:05,160 --> 03:33:08,960 SO IN DAY TWO WE WILL DETERMINE 4155 03:33:08,960 --> 03:33:12,960 RECEPTION TO VAGAL AND SO OUR 4156 03:33:12,960 --> 03:33:16,600 WALKING HYPOTHESIS IS THE 4157 03:33:16,600 --> 03:33:20,000 PROJECT INTO TMJ ACTUALLY 4158 03:33:20,000 --> 03:33:24,040 ELEVATES PAIN AND ALSO RECEPTION 4159 03:33:24,040 --> 03:33:27,160 TO SIGNALING AND TMJ AND SO WE 4160 03:33:27,160 --> 03:33:29,440 WILL WILL TERM THE ROLE OF THE 4161 03:33:29,440 --> 03:33:34,760 DOPAMINE RELEASED FROM THE VAGUS 4162 03:33:34,760 --> 03:33:36,640 AND WE WILL NOW HAVE THAT 4163 03:33:36,640 --> 03:33:42,280 BEHAVIOR AND PERFORM IN VIVO 4164 03:33:42,280 --> 03:33:43,800 GANGLION NEURON AND THE 4165 03:33:43,800 --> 03:33:46,840 ACTIVATIONAL DOPAMINE. 4166 03:33:46,840 --> 03:33:51,240 FOR AIM 3, OUR MULTI P.I. HERE 4167 03:33:51,240 --> 03:33:54,920 IN HE AND HIS TEAM WILL 4168 03:33:54,920 --> 03:33:57,840 DETERMINE CENTRAL VAGAL 4169 03:33:57,840 --> 03:34:00,880 ANESTHESIAIA FOR TMJ PAIN SO OUR 4170 03:34:00,880 --> 03:34:06,600 WALKING IS THAT VAGAL INPUT INTO 4171 03:34:06,600 --> 03:34:09,040 NTS NUKELIAL WHICH IS THE 4172 03:34:09,040 --> 03:34:12,080 CENTRAL FROM (INAUDIBLE) AND THE 4173 03:34:12,080 --> 03:34:14,480 PAIN TO A DIRECT PROJECTION OF 4174 03:34:14,480 --> 03:34:17,760 NTS NEURONS TO DIFFERENT BRAIN 4175 03:34:17,760 --> 03:34:21,360 REGIONS AND INVOLVED IN AFFECTED 4176 03:34:21,360 --> 03:34:23,560 TRANSMISSION AND PAIN MODULATION 4177 03:34:23,560 --> 03:34:26,000 AND SO THE ACTIVATION TEST 4178 03:34:26,000 --> 03:34:30,400 NEURON ASSOCIATED WITH THE VAGAL 4179 03:34:30,400 --> 03:34:31,960 STIMULATION PAIN AND ALSO THE 4180 03:34:31,960 --> 03:34:36,000 NTS NEURON THAT IS PROJECTED TO 4181 03:34:36,000 --> 03:34:38,960 THE CRITICAL FOR EFFECTING PAIN 4182 03:34:38,960 --> 03:34:41,640 AND ALSO THE PAIN (INAUDIBLE) SO 4183 03:34:41,640 --> 03:34:48,760 WE FOUND THAT THERE IS VAGAL ON 4184 03:34:48,760 --> 03:34:55,680 THOSE COMMON IN THIS TMJ AREA SO 4185 03:34:55,680 --> 03:35:06,440 YOU CAN SEE CORE THE OR I C TMJT 4186 03:35:07,360 --> 03:35:08,760 TO THIS EAR AREA AND OVER THE 4187 03:35:08,760 --> 03:35:11,960 BONE AND FROM THE TMJ AND IT'S 4188 03:35:11,960 --> 03:35:13,480 ACTUALLY HAVING THESE RED COLOR 4189 03:35:13,480 --> 03:35:16,080 ON THE RECEPTORS AND THEY 4190 03:35:16,080 --> 03:35:25,880 ACTUALLY INTERSECT SO WE HAVE 4191 03:35:25,880 --> 03:35:34,240 THIS RELEASED DOPAMINE AND YOU 4192 03:35:34,240 --> 03:35:36,400 SEE THIS CENTRAL PATHWAYS SO I 4193 03:35:36,400 --> 03:35:39,640 WAS REALLY SURPRISED TODAY THAT 4194 03:35:39,640 --> 03:35:44,240 ALL THE PHYSIOLOGICAL BRAIN 4195 03:35:44,240 --> 03:35:46,400 REGION TO THE PAIN EFFECTIVE 4196 03:35:46,400 --> 03:35:53,000 PATHWAYS AND SO YOU CAN SEE, WE 4197 03:35:53,000 --> 03:35:57,840 SEE IT GOES TO AND THIS ALL US 4198 03:35:57,840 --> 03:36:07,560 AND ACC AND SENSITIVE ORGANIZE 4199 03:36:07,560 --> 03:36:18,040 TEXT AND AND ALSO WE PRODUCT 4200 03:36:21,080 --> 03:36:25,800 POCKETS AND IT'S PAIN AND IT IS 4201 03:36:25,800 --> 03:36:29,920 IN THE PRIMARY EFFORT BY THE 4202 03:36:29,920 --> 03:36:35,920 MEET EIGHT OR AND THERE'S STILL 4203 03:36:35,920 --> 03:36:38,160 TO SIGNALING FROM THE VAGAL 4204 03:36:38,160 --> 03:36:40,280 NEURON TO THE PRIMARY SENSORY 4205 03:36:40,280 --> 03:36:43,000 AND IT'S VERY NOVEL AND SO NOW 4206 03:36:43,000 --> 03:36:45,880 WE PERFORM IN VIVO AND YOU CAN 4207 03:36:45,880 --> 03:36:49,440 CATCH AND TRY GANGLION NEURON 4208 03:36:49,440 --> 03:36:53,880 AND' USED THE MULTI LINE IN 4209 03:36:53,880 --> 03:36:57,560 VAGAL AND AND LABELED AND ALSO 4210 03:36:57,560 --> 03:36:59,280 WE ACTUAL DEPENDS ON LABELING ON 4211 03:36:59,280 --> 03:37:04,960 BRAIN NEURON AND AND ALSO WE DO 4212 03:37:04,960 --> 03:37:08,480 THE GENETIC OPERATIONS AND SO WE 4213 03:37:08,480 --> 03:37:11,640 DO TWO LAB COLLABORATIONS AND 4214 03:37:11,640 --> 03:37:17,160 Dr. KIM WHICH IS ME AND ALSO 4215 03:37:17,160 --> 03:37:20,640 Dr. CHUNG WE USED OUR 4216 03:37:20,640 --> 03:37:21,960 EXPERTISE FOR THIS AND THE 4217 03:37:21,960 --> 03:37:27,560 FOURTH WE INJECT CFA WHICH IS TO 4218 03:37:27,560 --> 03:37:30,800 TMJ AND IT CAN INDUDES 4219 03:37:30,800 --> 03:37:32,320 MECHANICAL HYPER TENSE TEE AND 4220 03:37:32,320 --> 03:37:36,480 YOU CAN SEE HERE IN THE MEANS 4221 03:37:36,480 --> 03:37:40,200 THAT ANIMAL SHARING A LOT OF 4222 03:37:40,200 --> 03:37:42,000 EXPERTISE MEANS THAT A LOT OF 4223 03:37:42,000 --> 03:37:44,360 PAIN AND THEN WE EXPLODED THE 4224 03:37:44,360 --> 03:37:47,840 VAGAL IN CHECK THE AREA AND THEN 4225 03:37:47,840 --> 03:37:54,160 ELECTRIC STILL WE CAN SEE THIS 4226 03:37:54,160 --> 03:37:57,240 PAIN AND YOU CAN SEE IN THE 4227 03:37:57,240 --> 03:37:58,880 BLUE, AFTER THE VAGAL 4228 03:37:58,880 --> 03:38:03,000 STIMULATION WE CAN SEE WE CAN GO 4229 03:38:03,000 --> 03:38:04,680 DRAMATICALLY REDUCED AND IT'S 4230 03:38:04,680 --> 03:38:06,520 BEEN FOR SEVERAL DAYS AND THEN 4231 03:38:06,520 --> 03:38:10,640 WE BUILDUP THE NEW MOUSE MODEL 4232 03:38:10,640 --> 03:38:15,440 WHICH IS CALLED FORCE OPENING 4233 03:38:15,440 --> 03:38:25,960 MODEL AND AS YOU CAN SEE HERE. 4234 03:38:30,760 --> 03:38:41,160 IT LASTS ABOUT AND FORCE NOT 4235 03:38:47,960 --> 03:38:50,560 OPENING AND THIS ACTUALLY DIS 4236 03:38:50,560 --> 03:38:51,720 LOCATES THE ENTER POSITION TO 4237 03:38:51,720 --> 03:38:55,800 WHICH ACTUALLY IN THIS VERY 4238 03:38:55,800 --> 03:38:59,440 STRONG PAIN AND AREA AND THEN WE 4239 03:38:59,440 --> 03:39:02,320 CHECK THE BY FORCE ANIMAL 4240 03:39:02,320 --> 03:39:03,400 ACTUALLY BY WE WILL AND BECAUSE 4241 03:39:03,400 --> 03:39:06,560 OF THE THE PAIN AND SO IT CAN 4242 03:39:06,560 --> 03:39:08,480 LAST ABOUT THREE WEEKS AND ALSO 4243 03:39:08,480 --> 03:39:11,880 WE CHECKED THE ANIMAL FACIAL 4244 03:39:11,880 --> 03:39:14,520 PAIN EXPRESSION AND CALLED IT 4245 03:39:14,520 --> 03:39:18,520 AND IT'S LIKE 20 DAYS AND THEY 4246 03:39:18,520 --> 03:39:21,440 CHECKED WITH THE CFA MODEL AND 4247 03:39:21,440 --> 03:39:24,360 OPEN FIELD TEST AND THE ANIMAL 4248 03:39:24,360 --> 03:39:28,000 AND THERE'S A HYPER WORKING 4249 03:39:28,000 --> 03:39:29,120 ACTIVITY WITH THE INFORMATION 4250 03:39:29,120 --> 03:39:34,400 NOW WE ARE TESTING THE CONDITION 4251 03:39:34,400 --> 03:39:35,440 PREFERENCE TEST TO SEE IF THEY 4252 03:39:35,440 --> 03:39:37,720 HAVE ANY PREFERENCE WITHOUT THIS 4253 03:39:37,720 --> 03:39:48,240 PAIN AND WE FOUND THIS DDC AND 4254 03:39:48,720 --> 03:39:53,160 IT'S HIGH IN NEURONS AND SO THIS 4255 03:39:53,160 --> 03:39:56,600 IS ACTUALLY CRITICAL TO MAKING 4256 03:39:56,600 --> 03:40:00,160 THE DOPAMINE IN THE BODY AND SO 4257 03:40:00,160 --> 03:40:06,760 WE INJECT A RETROGRADED RED DYE 4258 03:40:06,760 --> 03:40:10,240 INTO THE TMJ AND THERE'S A LOT 4259 03:40:10,240 --> 03:40:13,000 OF VAGAL LABELING THIS RED DYE 4260 03:40:13,000 --> 03:40:16,480 SO THIS MEANS THAT VAGAL 4261 03:40:16,480 --> 03:40:19,800 ACTUALLY INNOVATING TO THE TMJ 4262 03:40:19,800 --> 03:40:23,280 AND THEN ANOTHER RETROGRADE DYE 4263 03:40:23,280 --> 03:40:28,240 THROUGH OUR INJECTED AND THEN A 4264 03:40:28,240 --> 03:40:30,280 STANDARD DVC AND YOU CAN SEE 4265 03:40:30,280 --> 03:40:36,040 THERE'S MANY VAGAL OVERLAPPED 4266 03:40:36,040 --> 03:40:41,240 WITH THIS MEANS THAT THE TMJ 4267 03:40:41,240 --> 03:40:44,440 NEURONS WHICH IS THE NEURONS 4268 03:40:44,440 --> 03:40:49,080 FROM VAGAL AND THEN AFTER WE 4269 03:40:49,080 --> 03:40:52,040 MAKE FMO WE INJECT DOPAMINE SO 4270 03:40:52,040 --> 03:40:55,240 WHEN WE INJECT THE DOPAMINE INTO 4271 03:40:55,240 --> 03:40:57,480 TMJ WE CAN SEE OUR PAIN AND WE 4272 03:40:57,480 --> 03:40:59,000 CAN REPEAT THESE SEVERAL TIMES 4273 03:40:59,000 --> 03:41:01,840 AND THEN WE TROY TO IMAGE IN 4274 03:41:01,840 --> 03:41:05,120 VIVO THIS PRIMARY SENSORY 4275 03:41:05,120 --> 03:41:06,760 NEURON, ESPECIALLY WITH A NEURON 4276 03:41:06,760 --> 03:41:16,880 IS WE MADE THIS CALLED IT 4277 03:41:16,880 --> 03:41:20,440 CREATING POINT SO THE POT 4278 03:41:20,440 --> 03:41:21,960 ACTUALLY DRIVES THIS EXPRESSION 4279 03:41:21,960 --> 03:41:25,280 SO WHY WE CHOSE POT BECAUSE POT 4280 03:41:25,280 --> 03:41:27,520 IS ONLY EXCLUSIVELY EXPRESSED IN 4281 03:41:27,520 --> 03:41:30,920 PRIMARY SENSORY AND NOT IN ANY 4282 03:41:30,920 --> 03:41:33,800 OTHER BRAIN SO WE CAN HAVE A 4283 03:41:33,800 --> 03:41:34,960 VERY STRONG EXPRESSION AND ONLY 4284 03:41:34,960 --> 03:41:38,640 IN PRIMARY SENSORY NEURONS IS WE 4285 03:41:38,640 --> 03:41:43,880 CAN DO A LOT OF PAIN MODELING. 4286 03:41:43,880 --> 03:41:47,760 MIGRAINE, HEADACHE AND TRY THE 4287 03:41:47,760 --> 03:41:50,960 TMJ AND PAIN HERE AND ALSO TOOTH 4288 03:41:50,960 --> 03:41:53,720 PAIN AND ORAL FACIAL PAIN. 4289 03:41:53,720 --> 03:41:56,480 THE TWO IMAGES WE PURCHASED THIS 4290 03:41:56,480 --> 03:42:00,360 NICE HIGH REGULATION UNDER THIS 4291 03:42:00,360 --> 03:42:04,280 WE MADE A CUSTOM THIS PLATFORM 4292 03:42:04,280 --> 03:42:07,520 AND SO IN THE PLATFORM ANIMAL IS 4293 03:42:07,520 --> 03:42:11,560 LAID DOWN AND ANIMAL'S HEAD IS 4294 03:42:11,560 --> 03:42:16,520 HOLD O HE CAN MINIMIZE ANIMAL 4295 03:42:16,520 --> 03:42:21,320 MOVEMENT ARROWS. 4296 03:42:21,320 --> 03:42:26,000 IT STABILIZED ANIMAL BODY 4297 03:42:26,000 --> 03:42:27,360 TEMPERATURE AND THE WE HAVE A 4298 03:42:27,360 --> 03:42:31,480 VERY TINY CRANIAL RENAL TO LET 4299 03:42:31,480 --> 03:42:35,960 IT WE MADE A HOLE SO BY CORTICAL 4300 03:42:35,960 --> 03:42:40,880 TISSUE AND SO THEN, LET'S MOVE 4301 03:42:40,880 --> 03:42:45,360 ON, SO THEN, AS YOU CAN SEE 4302 03:42:45,360 --> 03:42:48,520 HERE, ALL THROUGH THE CRANIAL 4303 03:42:48,520 --> 03:42:53,440 WINDOW YOU CAN REACH OUT TO THE 4304 03:42:53,440 --> 03:42:54,840 LOCATED UNDER THE BRAIN AREA AND 4305 03:42:54,840 --> 03:42:59,800 WE CAN FOR THE FIRST TIME CAN 4306 03:42:59,800 --> 03:43:02,400 HAVE 3,000 NEURONS 4307 03:43:02,400 --> 03:43:04,320 SIMULTANEOUSLY SO WE CAN IMAGE 4308 03:43:04,320 --> 03:43:09,520 IT OVER HERE A TINY SMALL SIDE 4309 03:43:09,520 --> 03:43:11,040 CALLED RE SCEPTERS AND THEY CAN 4310 03:43:11,040 --> 03:43:17,600 SENSE PAIN AND WE CAN IMAGE IT 4311 03:43:17,600 --> 03:43:23,520 WHICH WE CAN TOUCH AND WE V1 OR 4312 03:43:23,520 --> 03:43:26,040 T AND P AND WE CAN EASILY 4313 03:43:26,040 --> 03:43:33,560 IDENTIFY AND THEN USING THIS 4314 03:43:33,560 --> 03:43:43,120 TOOL, 4315 03:43:43,120 --> 03:43:45,680 THERE'S A LOT GOING ON AFTER 4316 03:43:45,680 --> 03:43:48,560 THIS FMO AND THEN WE APPLIED 4317 03:43:48,560 --> 03:43:53,400 DOPAMINE ON TOP OF THIS AS YOU 4318 03:43:53,400 --> 03:43:59,560 CAN SEE THIS ACTUALLY IS HERE. 4319 03:43:59,560 --> 03:44:01,560 AND THEN WE ACTUAL LOW ALSO 4320 03:44:01,560 --> 03:44:07,160 INJECTED A CFA INTO THE TMJ AND 4321 03:44:07,160 --> 03:44:10,840 WE GET THE ACTIVITY AND THE CFA 4322 03:44:10,840 --> 03:44:13,440 AND THE ANIMAL YOU SEE THERE'S A 4323 03:44:13,440 --> 03:44:15,720 LOT OF THIS SPONTANEOUS GOING ON 4324 03:44:15,720 --> 03:44:20,200 AND COMPARED TO SHAM AND AFTER 4325 03:44:20,200 --> 03:44:23,880 WE SEE THIS SPONTANEOUS 4326 03:44:23,880 --> 03:44:26,000 ACTIVITY, WE ARE APPLYING 4327 03:44:26,000 --> 03:44:27,800 DOPAMINE WE CAN ALLEVIATE THIS 4328 03:44:27,800 --> 03:44:29,120 SPONTANEOUS ACTIVITY AND WE 4329 03:44:29,120 --> 03:44:31,800 TRIED TO DO A TRAP ON THIS 4330 03:44:31,800 --> 03:44:36,640 NEURON AND IT'S THE VAGAL NEURON 4331 03:44:36,640 --> 03:44:39,240 ACTUALLY HAVING THIS CENTRAL 4332 03:44:39,240 --> 03:44:44,720 TERMINAL USING THE FORCE BY ON 4333 03:44:44,720 --> 03:44:47,120 TEE GENETICS AND ALSO A 4334 03:44:47,120 --> 03:44:49,240 COMMUNITY ACTIVATION FOR THE 4335 03:44:49,240 --> 03:44:52,440 FIRST STEP AND WE EXPLODED THE 4336 03:44:52,440 --> 03:44:53,840 VAGAL AND ELECTRICALLY STIMULATE 4337 03:44:53,840 --> 03:44:57,080 AND THEN WE GET THE NTS AREA 4338 03:44:57,080 --> 03:45:03,920 HERE YOU CAN SEE THERE ARE 4339 03:45:03,920 --> 03:45:05,800 POSITIVE NEURONS THAT WE CAN 4340 03:45:05,800 --> 03:45:09,680 IDENTIFY HERE AND WE ALSO 4341 03:45:09,680 --> 03:45:13,600 ACTIVATE THE VAGAL CELL IN 4342 03:45:13,600 --> 03:45:16,040 MOLECULAR AREA AND WE LOCK AT 4343 03:45:16,040 --> 03:45:19,480 THE NTS AREA YOU CAN SEE A LOT 4344 03:45:19,480 --> 03:45:21,600 OF THE NEURONS AND WE CAN 4345 03:45:21,600 --> 03:45:24,240 IDENTIFY AND WE CAN SEE HERE SO 4346 03:45:24,240 --> 03:45:27,360 NEXT STAGE OF WE WANT TO USE THE 4347 03:45:27,360 --> 03:45:37,880 FIRST TREE TO ACTUALLY LABEL AND 4348 03:45:42,840 --> 03:45:44,640 THE CORTEX AREA. 4349 03:45:44,640 --> 03:45:46,480 I WOULD LIKE TO THANK OUR LAB 4350 03:45:46,480 --> 03:45:48,080 MEMBERS AND OUR PI. 4351 03:45:48,080 --> 03:45:50,920 AND HIS TEAM AND I WOULD LIKE TO 4352 03:45:50,920 --> 03:45:53,320 THANK ALL OUR COLLABORATORS ASK 4353 03:45:53,320 --> 03:45:55,160 AND I WOULD LIKE TO THANK OUR 4354 03:45:55,160 --> 03:45:55,800 FUNDING SOURCE. 4355 03:45:55,800 --> 03:45:57,480 THANK YOU, VERY MUCH. 4356 03:45:57,480 --> 03:46:04,480 [APPLAUSE] 4357 03:46:04,480 --> 03:46:06,880 >>ANY QUESTIONS? 4358 03:46:06,880 --> 03:46:10,400 I ASK ASK A QUICK ONE. 4359 03:46:10,400 --> 03:46:13,960 YOU MIGHT BE AWARE OF 4360 03:46:13,960 --> 03:46:16,440 NON-INVASIVE STIMULATION OF THE 4361 03:46:16,440 --> 03:46:19,840 OR I CAN YOU LAR BRANCH THE 4362 03:46:19,840 --> 03:46:21,920 VAGUS HAVE BEEN USED FOR CARDIAC 4363 03:46:21,920 --> 03:46:22,280 APPLICATIONS. 4364 03:46:22,280 --> 03:46:26,480 I'M JUST CURIOUS IF YOU THINK A 4365 03:46:26,480 --> 03:46:28,560 NON-INVASIVE APPROACH OF A 4366 03:46:28,560 --> 03:46:29,680 TEMPORAL NERVE COULD BE 4367 03:46:29,680 --> 03:46:31,120 SIMILARLY USED TO ACTUALLY 4368 03:46:31,120 --> 03:46:32,400 SUPPRESS PAIN GIVEN THE CIRCUIT 4369 03:46:32,400 --> 03:46:33,640 YOU ARE DESCRIBING? 4370 03:46:33,640 --> 03:46:35,760 >>THAT'S REALLY GOOD QUESTION 4371 03:46:35,760 --> 03:46:40,960 SOLSO WE ACTUALLY -- I HONESTLYI 4372 03:46:40,960 --> 03:46:46,040 DIDN'T KNOW THERE WAS ACTUALLY 4373 03:46:46,040 --> 03:46:48,280 (INAUDIBLE) BUT YEAH, WE WILL 4374 03:46:48,280 --> 03:46:50,280 TRY TO INDIFFERENT SPECIFIC 4375 03:46:50,280 --> 03:46:54,280 SUBSET AREAS TO ACTIVATE IT. 4376 03:46:54,280 --> 03:46:56,800 THANK YOU. 4377 03:46:56,800 --> 03:46:59,000 LAST TALK Dr. COSTA. 4378 03:46:59,000 --> 03:47:01,120 >>HI, THERE, EVERYONE. 4379 03:47:01,120 --> 03:47:03,560 IT'S REALLY A PLEASURE TO BE 4380 03:47:03,560 --> 03:47:05,320 HERE AND I'VE BEEN LEARNING A 4381 03:47:05,320 --> 03:47:06,640 LOT AND THERE'S A LOT OF 4382 03:47:06,640 --> 03:47:10,120 QUESTIONS AND THIS IS VERY 4383 03:47:10,120 --> 03:47:12,760 EXCITING AND SO TODAY I'M GOING 4384 03:47:12,760 --> 03:47:18,040 TO TALK ABOUT THE PART OF 4385 03:47:18,040 --> 03:47:20,440 CONTROL AS WE HEARD ALREADY A 4386 03:47:20,440 --> 03:47:22,080 LITTLE BIT AND ABOUT THE 4387 03:47:22,080 --> 03:47:23,040 DESCENDING INNERRIZATION AND 4388 03:47:23,040 --> 03:47:28,400 CONTROL OF INTERNAL ORGAN 4389 03:47:28,400 --> 03:47:30,160 FUNCTION. 4390 03:47:30,160 --> 03:47:40,560 OUR LAB AND THERE WE GO. 4391 03:47:50,760 --> 03:47:53,960 OUR LAB AND MUCH OF THE WORLD 4392 03:47:53,960 --> 03:47:57,400 HAS BEEN STUDYING ANIMAL 4393 03:47:57,400 --> 03:48:00,120 BEHAVIOR IN THE OVERT SENSE AND 4394 03:48:00,120 --> 03:48:02,720 ALSO HOW ANIMALS LEARN TO 4395 03:48:02,720 --> 03:48:04,480 CONTROL WHICH BEHAVIOR, WHICH 4396 03:48:04,480 --> 03:48:07,440 MOVEMENT IS APPROPRIATE IN A 4397 03:48:07,440 --> 03:48:09,800 PARTICULAR CONTEXT OR UPON 4398 03:48:09,800 --> 03:48:17,800 CERTAIN SYSTEMS AND WE KNOW FOR 4399 03:48:17,800 --> 03:48:19,160 BODILY MOVEMENTS OF THE MAIN 4400 03:48:19,160 --> 03:48:29,840 BODY IT'S THE INN INAND THEY'RE 4401 03:48:31,680 --> 03:48:32,440 QUIETLY TIGHTLY CONTROLLED IN 4402 03:48:32,440 --> 03:48:35,560 THE SPINAL CORD AND THAT IT CAN 4403 03:48:35,560 --> 03:48:40,400 INNOVATE MUSCLES, FROM MOVEMENT 4404 03:48:40,400 --> 03:48:44,360 AND MEDIATE REFLEX MOVEMENT SO 4405 03:48:44,360 --> 03:48:47,000 FOR VOLUNTARY MOVEMENTS WE NEED 4406 03:48:47,000 --> 03:48:52,280 THE DESCENDING INPUT FROM THE 4407 03:48:52,280 --> 03:48:56,280 BRAIN AND A LOT OF INPUT TO THE 4408 03:48:56,280 --> 03:48:59,360 EXECUTIVE AND WE KNOW THAT THIS 4409 03:48:59,360 --> 03:49:01,000 IS SPECIFIC POPULATION THAT 4410 03:49:01,000 --> 03:49:04,240 INNOVATED THE SPINAL SPECIFIC 4411 03:49:04,240 --> 03:49:08,360 SPINAL CIRCUITS TO SPECIFIC 4412 03:49:08,360 --> 03:49:13,400 MUSCLE CONTROL PATTERNS AND WE 4413 03:49:13,400 --> 03:49:15,200 HAVE ALSO FOUND CORTICAL INPUT 4414 03:49:15,200 --> 03:49:17,960 TO SPINAL CORD IS PERHAPS LARGER 4415 03:49:17,960 --> 03:49:19,840 THAN WE PREVIOUSLY ACKNOWLEDGED 4416 03:49:19,840 --> 03:49:23,360 AND ALSO SPECIFIC POPULATIONS OF 4417 03:49:23,360 --> 03:49:34,160 COURTI CANAL NEURONS AND TO REIE 4418 03:50:12,840 --> 03:50:14,720 AND CIRCUITS AND INDUCED OR 4419 03:50:14,720 --> 03:50:17,040 WANGING INDUCES PLASTIC TEE AND 4420 03:50:17,040 --> 03:50:22,720 THIS IS FOR OVERT BEHAVIOR BUT A 4421 03:50:22,720 --> 03:50:26,760 LOT OF WHAT WE CONSIDER BEHAVIOR 4422 03:50:26,760 --> 03:50:30,000 IN NEURAL SPACE IS NOT ONLY 4423 03:50:30,000 --> 03:50:30,360 THROUGH MULLS. 4424 03:50:30,360 --> 03:50:33,200 IF I REACH FOR AN APPLE OR A 4425 03:50:33,200 --> 03:50:36,400 APPROACH A FOOD SOURCE AND WE 4426 03:50:36,400 --> 03:50:38,240 HEARD HERE AND I SHOULD BE 4427 03:50:38,240 --> 03:50:40,240 STARTING TO PREPARE FOR THE FACT 4428 03:50:40,240 --> 03:50:42,800 THAT I'M GOING TO GET IMMUNE AND 4429 03:50:42,800 --> 03:50:44,920 WE KNOW THAT ALSO THERE'S 4430 03:50:44,920 --> 03:50:46,720 DESCENDING INNERRIZATION OF 4431 03:50:46,720 --> 03:50:51,960 OTHER ORGANS AND THE PAN 4432 03:50:51,960 --> 03:50:53,720 CREATION THAT WE'LL START 4433 03:50:53,720 --> 03:50:55,960 INCREASING THE RELEASE OF 4434 03:50:55,960 --> 03:50:58,600 INSULIN AND DECREASE THE RELEASE 4435 03:50:58,600 --> 03:51:01,160 OF NOT ONLY THAT REFLECTIVELY 4436 03:51:01,160 --> 03:51:04,560 AFTER YOU EAT BUT WITH TIME IN 4437 03:51:04,560 --> 03:51:06,800 PREPARATION FOR THE MEAL AND FOR 4438 03:51:06,800 --> 03:51:11,120 EXAMPLE, THE DESCENDING 4439 03:51:11,120 --> 03:51:21,680 INNOVATION OF THE SPLEEN AND AND 4440 03:51:23,160 --> 03:51:25,000 WE KNOW A LITTLE BIT ABOUT THE 4441 03:51:25,000 --> 03:51:26,640 HYPOTHALIMUS AND THE REGIONS, 4442 03:51:26,640 --> 03:51:29,320 ARE IMPORTANT FOR THESE AND WE 4443 03:51:29,320 --> 03:51:33,160 WANTED TO TAKE A MORE SYSTEMATIC 4444 03:51:33,160 --> 03:51:37,120 APPROACH TO THESE AND SO THERE 4445 03:51:37,120 --> 03:51:39,000 ARE -- FIRST, HOW DO WE STUDIES 4446 03:51:39,000 --> 03:51:41,520 THOSE CONTROL OF INTERNAL ORGAN 4447 03:51:41,520 --> 03:51:43,400 FUNCTIONS FOR PREDICTIVE CONTROL 4448 03:51:43,400 --> 03:51:45,520 OF PAN CROW ATTIC FUNCTION AND 4449 03:51:45,520 --> 03:51:49,040 THIS RELEASE OF INSULIN AND 4450 03:51:49,040 --> 03:51:51,840 DECREASED THAT WE'VE SEEN WE CAN 4451 03:51:51,840 --> 03:51:54,560 USE PAVLOVIAN CONTINUING THAT 4452 03:51:54,560 --> 03:51:58,040 HAS BEEN AROUND FOR 100 YEARS 4453 03:51:58,040 --> 03:51:59,680 AND PAVLOV HAD A LOT OF INSIGHTS 4454 03:51:59,680 --> 03:52:03,920 TO THESE WHERE YOU PRESENT A 4455 03:52:03,920 --> 03:52:07,720 NEUTRAL STIMULUS PREPARED FOR A 4456 03:52:07,720 --> 03:52:09,960 CERTAIN FOOD FOR EXAMPLE, 4457 03:52:09,960 --> 03:52:12,960 SUCROSE AND JUST PREVENTING OF 4458 03:52:12,960 --> 03:52:14,880 THAT CONTINUE STIMULUS OR 4459 03:52:14,880 --> 03:52:16,400 CONTINUAL STIMULUS AS IT SHOULD 4460 03:52:16,400 --> 03:52:18,240 BE AND I WILL IS ITS ACTUALLY 4461 03:52:18,240 --> 03:52:20,760 THE PHYSIOLOGICAL RESPONSE EVEN 4462 03:52:20,760 --> 03:52:24,040 IN THE ABSENCE OR AHEAD OF FOOD. 4463 03:52:24,040 --> 03:52:25,400 AND THIS IS WELL-KNOWN AND 4464 03:52:25,400 --> 03:52:29,480 PERHAPS NOT SURPRISING BUT YOU 4465 03:52:29,480 --> 03:52:31,400 KNOW, WHAT IS INTERESTING IS 4466 03:52:31,400 --> 03:52:33,680 THIS IS MUCH MORE GENERALIZABLE 4467 03:52:33,680 --> 03:52:36,680 SO FOR EXAMPLE, NOW, IF YOU PAIR 4468 03:52:36,680 --> 03:52:42,280 A PARTICULAR CONTINUAL STIMULUS 4469 03:52:42,280 --> 03:52:45,560 LET'S SAY SACCHARIN, WHICH IS AN 4470 03:52:45,560 --> 03:52:47,080 IMMUNOSUPPRESS ENTER FOR A 4471 03:52:47,080 --> 03:52:49,120 WHILE, THEN YOU CAN PRESENT JUST 4472 03:52:49,120 --> 03:52:51,000 THE CONDITIONAL STIMULUS AND 4473 03:52:51,000 --> 03:52:55,000 JUST THE CS AND THAT IS 4474 03:52:55,000 --> 03:52:57,240 SUFFICIENT TO GET A CONDITION 4475 03:52:57,240 --> 03:53:01,440 IMMUNO SUPPRESSION IN RESPONSE 4476 03:53:01,440 --> 03:53:04,280 TO FOR EXAMPLE INJECTIONS WITH 4477 03:53:04,280 --> 03:53:04,520 LPS. 4478 03:53:04,520 --> 03:53:08,120 SO THESE, WE KNOW, REQUIRES 4479 03:53:08,120 --> 03:53:13,120 DESCENDING INO INNOVATION AND 4480 03:53:13,120 --> 03:53:15,480 THERE'S STUDIES OF THE HIPPO 4481 03:53:15,480 --> 03:53:19,360 THALAMUS AND THE INNOVATION OF 4482 03:53:19,360 --> 03:53:29,720 SPLEEN IN THIS CASE. 4483 03:53:53,480 --> 03:53:55,320 AND PANCREAS AND SPLEEN AND 4484 03:53:55,320 --> 03:53:57,440 THESE ARE TH POSITIVE NEURONS 4485 03:53:57,440 --> 03:54:01,240 AND YOU SEE THE PANCREAS MORE 4486 03:54:01,240 --> 03:54:03,520 DIFFUSED AND IN THE SPLEEN AND 4487 03:54:03,520 --> 03:54:06,960 IT'S MORE ORGANIZED AND IT IS 4488 03:54:06,960 --> 03:54:11,880 JUST MARVELOUS TO LOOK AT THESE 4489 03:54:11,880 --> 03:54:15,960 ORGANIZATIONS AND SO THESE 4490 03:54:15,960 --> 03:54:21,200 INNOVATIONS COMES FROM THE 4491 03:54:21,200 --> 03:54:23,760 GANGLION AND ONE THE FIRST 4492 03:54:23,760 --> 03:54:25,760 EXPERIMENT WAS INJECTED ALCOHOL 4493 03:54:25,760 --> 03:54:28,640 TOXIN B WITH DIFFERENT COLORS IN 4494 03:54:28,640 --> 03:54:31,320 SPLEEN AND PANCREAS AND LOCK AT 4495 03:54:31,320 --> 03:54:36,360 THE CELL BODIES IN CMG THAT WERE 4496 03:54:36,360 --> 03:54:38,000 INNERVATING THESE TWO ORGANS AND 4497 03:54:38,000 --> 03:54:39,760 PERHAPS NOT SURPRISINGLY FOR 4498 03:54:39,760 --> 03:54:41,680 THIS CROWD HERE BUT CERTAINLY A 4499 03:54:41,680 --> 03:54:44,640 BIT SURPRISING FOR US WHEN WE 4500 03:54:44,640 --> 03:54:47,800 FIRST SAW IT, IT SEEMS THAT 4501 03:54:47,800 --> 03:54:49,680 THESE ARE MOSTLY DIFFERENT 4502 03:54:49,680 --> 03:54:52,320 POPULATIONS OF NEURONS WITHIN 4503 03:54:52,320 --> 03:54:55,160 CMG AND THERE'S SOME, IN THIS 4504 03:54:55,160 --> 03:54:58,360 FIELD, ONE NEURON, HAD POTENTIAL 4505 03:54:58,360 --> 03:55:01,200 LOW INNERVATED BOTH BUT IT SEEMS 4506 03:55:01,200 --> 03:55:04,800 THAT DIFFERENT POPULATIONS ARE 4507 03:55:04,800 --> 03:55:06,640 INNERVATING THIS TWO ORGANS AND 4508 03:55:06,640 --> 03:55:09,640 IT AGAIN COULD POINT TO THAT 4509 03:55:09,640 --> 03:55:12,880 GRANULARITY THAT WE WERE 4510 03:55:12,880 --> 03:55:16,280 SPEAKING ABOUT WHAT THEY WILL 4511 03:55:16,280 --> 03:55:19,160 BEEN DOING IN COLLABORATION AT 4512 03:55:19,160 --> 03:55:21,400 THE ALLEN INSTITUTION IS 4513 03:55:21,400 --> 03:55:22,960 ACTUALLY SEQUENCING THESE 4514 03:55:22,960 --> 03:55:25,400 NEURONS SO HOPEFULLY IT'S GOING 4515 03:55:25,400 --> 03:55:28,760 TO NOW ACTUALLY START OUR 4516 03:55:28,760 --> 03:55:31,480 SPECIFIC MOLECULAR IDENTITY. 4517 03:55:31,480 --> 03:55:35,640 AND THE NEXT STEP WHAT LEONE 4518 03:55:35,640 --> 03:55:37,680 O'ER WANTED TO KNOW WAS WHAT IS 4519 03:55:37,680 --> 03:55:42,040 THE INPUT TO THE GANGLION 4520 03:55:42,040 --> 03:55:48,480 NEURONS AND TO DO THESE, SHE 4521 03:55:48,480 --> 03:55:52,880 USED A CYTO TYPE OF RABIES BUT 4522 03:55:52,880 --> 03:55:56,920 IT DOESN'T JUMP BACK TO JUST 4523 03:55:56,920 --> 03:55:58,840 LABORED THE NEURONS THAT THE 4524 03:55:58,840 --> 03:56:01,960 AXONS OF AND WHAT SHE SAYS IS 4525 03:56:01,960 --> 03:56:05,120 THAT YOU KNOW, SHE HAD NEURONS 4526 03:56:05,120 --> 03:56:08,560 IN THE INTER IMMEDIATE LATERAL 4527 03:56:08,560 --> 03:56:11,960 COLON OF THE CORD AND THE INTER 4528 03:56:11,960 --> 03:56:19,240 ELECTED NUCLEUS BUT IT ALSO IF 4529 03:56:19,240 --> 03:56:20,960 SEEMS THAT THE INNOVATION FROM 4530 03:56:20,960 --> 03:56:25,360 THE SPINAL CORD IS ALSO NOT 4531 03:56:25,360 --> 03:56:35,760 COMING JUST IF THEY ARE 4532 03:56:48,560 --> 03:56:50,480 TARGETING THE TYPES AND WE DON'T 4533 03:56:50,480 --> 03:56:53,440 KNOW THAT YET AND SO, AFTER 4534 03:56:53,440 --> 03:56:57,320 MAPPING THE SECOND NEURONS, LEO 4535 03:56:57,320 --> 03:57:01,000 NOWHERE AND LINDA IN THE LAB AND 4536 03:57:01,000 --> 03:57:05,800 THESE EXPERIMENTS WHICH WAS NOW 4537 03:57:05,800 --> 03:57:07,960 AGAIN WITH THE RABIES AND NOW 4538 03:57:07,960 --> 03:57:10,920 COMPLIMENTING WITH THE HELPER 4539 03:57:10,920 --> 03:57:13,360 THAT HAVE GLYCO PROTEIN IN THE 4540 03:57:13,360 --> 03:57:17,200 SPINAL CORD SO YOU GET THE THIRD 4541 03:57:17,200 --> 03:57:21,040 OR THE NEURONS WHICH ACTUALLY 4542 03:57:21,040 --> 03:57:23,360 INPUT TO THE CORD NEURONS THAT 4543 03:57:23,360 --> 03:57:26,680 THE GANGLIA AND WHAT WAS AMAZING 4544 03:57:26,680 --> 03:57:32,560 IS OF COURSE NOW USING SPINAL 4545 03:57:32,560 --> 03:57:36,400 WAS DEVELOPED BY THE DOCTOR AND 4546 03:57:36,400 --> 03:57:38,240 YOU COULD SEE WHERE VIRTUALLY 4547 03:57:38,240 --> 03:57:40,360 ALL CELL BODIES OR MANY OF THE 4548 03:57:40,360 --> 03:57:44,920 CELL BOD OTH BODIES ARE IN THE D 4549 03:57:44,920 --> 03:57:47,080 YOU SEE THE HYPOTHALAMUS BUT I 4550 03:57:47,080 --> 03:57:48,960 WANT TO DRAW YOUR ATTENTION TO 4551 03:57:48,960 --> 03:57:56,720 THE VERY STRONG CORTICAL INPUT D 4552 03:57:56,720 --> 03:57:58,760 YOU CAN SEE IT IN THE THE FIRST 4553 03:57:58,760 --> 03:58:00,000 TIME SLIDE AND COMING UP ONLY 4554 03:58:00,000 --> 03:58:02,160 FROM AREAS OF THE INSULIN FROM 4555 03:58:02,160 --> 03:58:06,680 THE COX TEXT WE SAW BUT IN CASE 4556 03:58:06,680 --> 03:58:11,160 FROM THE MOR MOTOR CORTEX WHERE 4557 03:58:11,160 --> 03:58:16,480 SEE THE TYPICAL CORTICAL SPINAL 4558 03:58:16,480 --> 03:58:18,720 TRACT AND THE SENSORY COURSES 4559 03:58:18,720 --> 03:58:21,840 AND WHICH ALSO, EVEN FOR MUSCLE 4560 03:58:21,840 --> 03:58:25,120 ALSO DESCENDING INPUT AND NOW, 4561 03:58:25,120 --> 03:58:27,440 SOME OF THESE AREAS ARE, WE 4562 03:58:27,440 --> 03:58:29,120 STILL NEED TO DO MORE CONTROLS 4563 03:58:29,120 --> 03:58:31,400 BUT THESE ARE AREAS OF THE 4564 03:58:31,400 --> 03:58:32,080 SPINAL CORD VERY DIFFERENT THAN 4565 03:58:32,080 --> 03:58:34,560 THE AREAS THAT ARE RESPONSIBLE 4566 03:58:34,560 --> 03:58:38,680 FOR MOTOR INNOVATION AND SO THIS 4567 03:58:38,680 --> 03:58:41,440 WAS EXCITING BUT SURPRISING SO 4568 03:58:41,440 --> 03:58:44,000 WE THOUGHT WHAT ABOUT OTHER 4569 03:58:44,000 --> 03:58:45,600 ORGANS THAT HAVE A LITTLE BIT OF 4570 03:58:45,600 --> 03:58:47,640 A DIFFERENT INNOVATION SO FOR 4571 03:58:47,640 --> 03:58:55,440 EXAMPLE, THE ADRENAL GLAND THAT 4572 03:58:55,440 --> 03:58:58,520 STORES EPINEPHRIN IT ALSO 4573 03:58:58,520 --> 03:59:00,320 RECEIVES INPUT FROM THE CORD BUT 4574 03:59:00,320 --> 03:59:02,440 DIRECT INPUT SO IT DOESN'T GO 4575 03:59:02,440 --> 03:59:08,400 NECESSARILY THROUGH A GANGLIA 4576 03:59:08,400 --> 03:59:14,720 AND SO, JOSH GROWN DID A SIMILAR 4577 03:59:14,720 --> 03:59:17,720 AND HERE YOU SEE AGAIN, MANY 4578 03:59:17,720 --> 03:59:28,240 CORTICAL NEURONS IN AND OTHERS 4579 03:59:31,680 --> 03:59:33,920 FOR THE TAKE OF TIME I'M LEAVE 4580 03:59:33,920 --> 03:59:35,760 IT FOR DISCUSS BUT HOW DO WE GO 4581 03:59:35,760 --> 03:59:37,400 ABOUT STUDYING THESE CONNECT WE 4582 03:59:37,400 --> 03:59:41,040 WANT TO LOOK THE ALL THE BRAIN 4583 03:59:41,040 --> 03:59:44,680 DESCENDING NEURONS BUT MAYBE WE 4584 03:59:44,680 --> 03:59:47,160 NEED TO START GOING FROM THE 4585 03:59:47,160 --> 03:59:52,480 PERIPHERY BACK AND SO, SHEERAN 4586 03:59:52,480 --> 03:59:56,520 EX FORMENT THAT THEY NEED AND 4587 03:59:56,520 --> 03:59:59,160 DOING ONE PHOTO IMAGING OF G 4588 03:59:59,160 --> 04:00:05,880 CAMP ACTIVITIES AND AFTER 4589 04:00:05,880 --> 04:00:10,840 INJECTION OF PLS AND I WANT TO 4590 04:00:10,840 --> 04:00:13,720 MAKE ONE POINT WHICH IS THERE 4591 04:00:13,720 --> 04:00:17,080 ARE A FEW NEURONS THAT DO 4592 04:00:17,080 --> 04:00:19,560 RESPOND MUCH BUT IF YOU HEAR THE 4593 04:00:19,560 --> 04:00:21,560 GREEN NEURONS THAT INCREASES IN 4594 04:00:21,560 --> 04:00:22,760 ACTIVITIES AND DAYS FOR A LONG 4595 04:00:22,760 --> 04:00:27,040 TIME AND THIS IS WHAT WE 4596 04:00:27,040 --> 04:00:30,160 TYPICALLY THINK OF OF THE 4597 04:00:30,160 --> 04:00:32,360 NERVOUS SYSTEM RESPONSE BUT FOR 4598 04:00:32,360 --> 04:00:33,600 EXAMPLE, THIS BLUE HAS A TRANCE 4599 04:00:33,600 --> 04:00:34,680 SEE ENTER HERE AND YOU WILL SEE 4600 04:00:34,680 --> 04:00:36,760 I MEAN THIS IS A SPED UP VIEW 4601 04:00:36,760 --> 04:00:41,280 BUT TOWARDS THE END OF THE 4602 04:00:41,280 --> 04:00:42,800 VIDEO, IT'S A TRANCE SEE ENTER 4603 04:00:42,800 --> 04:00:44,080 INCREASING ACTIVITY. 4604 04:00:44,080 --> 04:00:51,880 THIS IS HEAVILY MOTION 4605 04:00:51,880 --> 04:00:53,400 CORRECTED, YOU WILL SEE IT NOW, 4606 04:00:53,400 --> 04:00:53,760 BOOM. 4607 04:00:53,760 --> 04:00:59,520 GO UP AND SO THERE'S PATTERNS OF 4608 04:00:59,520 --> 04:01:00,040 ACTIVITIES THAT ARE VERY 4609 04:01:00,040 --> 04:01:02,080 DIFFERENT AND VERY CLOSE TO THE 4610 04:01:02,080 --> 04:01:04,400 PERIPHERY AND SO WE DO NEED TO 4611 04:01:04,400 --> 04:01:07,200 UNDERSTAND THESE PATTERNS AND IN 4612 04:01:07,200 --> 04:01:09,600 THE REFLECT OR THE HOMEOSTATIC 4613 04:01:09,600 --> 04:01:11,800 CONDITIONS BUT ALSO IN THE 4614 04:01:11,800 --> 04:01:12,600 LEARNED CONDITIONS AND OF 4615 04:01:12,600 --> 04:01:14,760 COURSE, I MEAN, WE, LIKE 4616 04:01:14,760 --> 04:01:19,040 EVERYONE HERE, WE HAVE BEEN MORE 4617 04:01:19,040 --> 04:01:21,040 METHODS TO ACTUALLY MEASURE AND 4618 04:01:21,040 --> 04:01:22,080 CONTROL THINGS WHEN YOU GET INTO 4619 04:01:22,080 --> 04:01:24,280 THE BRAIN AND EVEN BRAIN STEM 4620 04:01:24,280 --> 04:01:26,880 BUT I DO THINK THAT WE NEED TO 4621 04:01:26,880 --> 04:01:32,160 DEVELOP A LOT OF MORE METHODS TO 4622 04:01:32,160 --> 04:01:32,920 MEASURE THINGS AND CONTROL IN 4623 04:01:32,920 --> 04:01:35,240 THE PERIPHERY. 4624 04:01:35,240 --> 04:01:43,400 SO, WE WANT TO LEAVE A MESSAGE 4625 04:01:43,400 --> 04:01:44,600 HERE IS THAT MAYBE THESE MOTOR 4626 04:01:44,600 --> 04:01:46,720 SYSTEMS THAT WE TALK ABOUT 4627 04:01:46,720 --> 04:01:50,600 ACTUALLY DIDN'T EVOLVE ONLY TO 4628 04:01:50,600 --> 04:01:51,880 CONTROL MUSCLE WHICH WOULDN'T 4629 04:01:51,880 --> 04:01:53,120 MAKE SENSE AND WE HEARD ABOUT 4630 04:01:53,120 --> 04:01:54,960 THE SENSORY SYSTEMS THAT ARE 4631 04:01:54,960 --> 04:01:56,560 ACTUALLY SIMILAR BUT ARE 4632 04:01:56,560 --> 04:01:57,840 ACTUALLY CONTROLLED SYSTEMS AND 4633 04:01:57,840 --> 04:02:00,720 THEY CONTROL THE ADAPTIVE 4634 04:02:00,720 --> 04:02:01,920 BEHAVIOR OF THE ORGANISM AND 4635 04:02:01,920 --> 04:02:04,120 MAYBE BEFORE WE EVEN SENSE THE 4636 04:02:04,120 --> 04:02:06,000 INTERACTIVE WITH THE WORLD, AS 4637 04:02:06,000 --> 04:02:07,880 WE BECAME MULTI CELLULAR 4638 04:02:07,880 --> 04:02:09,920 ORGANISMS THROUGHOUT THE 4639 04:02:09,920 --> 04:02:11,320 EVOLUTION, THE MAIN 4640 04:02:11,320 --> 04:02:14,800 PREOCCUPATION OF THE NERVOUS 4641 04:02:14,800 --> 04:02:17,400 SYSTEM WAS A FAST SENSOR OF 4642 04:02:17,400 --> 04:02:20,120 THINGS INSIDE AND RESPONSES AND 4643 04:02:20,120 --> 04:02:28,400 THE BEAUTIFUL OF THE PAVLOVIAN 4644 04:02:28,400 --> 04:02:29,920 SYSTEM WHERE IT'S NOT JUST THE 4645 04:02:29,920 --> 04:02:31,000 CLOSE LOOK REFLEX. 4646 04:02:31,000 --> 04:02:33,360 NOW AN INPUT THROUGH AN EYE CAN 4647 04:02:33,360 --> 04:02:35,360 ACTUALLY CONNECT AND THE 4648 04:02:35,360 --> 04:02:36,440 ASSOCIATE THROUGH WHAT WE THINK 4649 04:02:36,440 --> 04:02:41,240 MAY BE THE REFLEX IS SYSTEM THAT 4650 04:02:41,240 --> 04:02:43,160 CONTROLS, YOU KNOW, METABOLISM 4651 04:02:43,160 --> 04:02:45,720 OR THE IMMUNE SYSTEMS SO, I 4652 04:02:45,720 --> 04:02:47,720 THINK THIS IS THE SUPER EXCITING 4653 04:02:47,720 --> 04:02:50,960 FOR NEUROSCIENCE AND I THINK 4654 04:02:50,960 --> 04:02:55,240 CONCEPTUALLY AND UNFORT LOW WHEN 4655 04:02:55,240 --> 04:02:59,520 WE READ PAVLOV HE GOT MOST OF IT 4656 04:02:59,520 --> 04:03:00,840 ALREADY BUT SOME OF THE NEW 4657 04:03:00,840 --> 04:03:03,280 TOOLS AND THIS COLLABORATIVE 4658 04:03:03,280 --> 04:03:05,080 EFFORT LIKE WHAT WE HAVE HERE 4659 04:03:05,080 --> 04:03:06,480 IT'S A PLEASURE. 4660 04:03:06,480 --> 04:03:09,560 I JUST WANT TO THANK EVERYONE IN 4661 04:03:09,560 --> 04:03:20,400 THE LAB AND IN PARTICULAR LOW IL 4662 04:03:23,240 --> 04:03:23,760 OF YOU. 4663 04:03:23,760 --> 04:03:27,120 [APPLAUSE] 4664 04:03:27,120 --> 04:03:28,400 THANK YOU Dr. COSTA. 4665 04:03:28,400 --> 04:03:30,720 ANY QUESTIONS? 4666 04:03:30,720 --> 04:03:34,600 >>THAT WAS GREAT. 4667 04:03:34,600 --> 04:03:37,440 SO, WE HAVE REALLY COOL 4668 04:03:37,440 --> 04:03:38,200 EXPERIMENTS SHOWING THAT 4669 04:03:38,200 --> 04:03:40,840 SPECIFIC DEEP LAYER NEURONS IN 4670 04:03:40,840 --> 04:03:44,520 MOTOR CORTEX DRIVE COMPLEX 4671 04:03:44,520 --> 04:03:45,800 HAND-TO-MOUTH BEHAVIOR SIMILAR 4672 04:03:45,800 --> 04:03:47,720 TO WHAT WAS SHOWN. 4673 04:03:47,720 --> 04:03:49,000 I WONDER WHETHER OR NOT LIKE 4674 04:03:49,000 --> 04:03:50,160 WHEN YOU ARE AT THE POINT WHERE 4675 04:03:50,160 --> 04:03:52,160 YOU HAVE A COMPLEX 4676 04:03:52,160 --> 04:03:55,600 HAPPENED-TO-MOUTH BEHAVIOR FOR 4677 04:03:55,600 --> 04:03:56,960 BRINGING FOOD TO YOUR MOUTH 4678 04:03:56,960 --> 04:03:59,520 WOULD YOU USE THE SAME NEURONS 4679 04:03:59,520 --> 04:04:03,920 TO CREATE INSULIN. 4680 04:04:03,920 --> 04:04:05,280 >>THIS IS A SUPER INTERESTING 4681 04:04:05,280 --> 04:04:05,560 QUESTION. 4682 04:04:05,560 --> 04:04:08,000 OF COURSE, I MEAN, I KNOW THIS 4683 04:04:08,000 --> 04:04:09,760 STUDIES AND WE'VE SUM YOU LATED 4684 04:04:09,760 --> 04:04:12,000 IN OTHER AREAS BUT WE 4685 04:04:12,000 --> 04:04:13,160 CONCEPTUALLY ALWAYS THOUGHT OF 4686 04:04:13,160 --> 04:04:16,600 IT AS DIFFERENT CIRCUITS THAT 4687 04:04:16,600 --> 04:04:19,680 WOULD BE COORDINATED INTO 4688 04:04:19,680 --> 04:04:19,920 SOMEWAY. 4689 04:04:19,920 --> 04:04:21,760 BUT AGAINST MY ANALOGY OF 4690 04:04:21,760 --> 04:04:23,920 REACHING FOR FOOD, BUT WOULDN'T 4691 04:04:23,920 --> 04:04:34,440 IT BE INTERESTING IF ACTUALLY SO 4692 04:04:39,480 --> 04:04:41,240 OBVIOUSLY IT'S NOT NECESSARILY 4693 04:04:41,240 --> 04:04:43,240 LEARNED AND IF WE GO INTO A 4694 04:04:43,240 --> 04:04:47,520 CERTAIN AREA OF THE BASAL 4695 04:04:47,520 --> 04:04:48,920 GANGLIA, WE IT FOR EXAMPLE 4696 04:04:48,920 --> 04:04:52,160 INDUCE THE WHOLE FACIAL MOVEMENT 4697 04:04:52,160 --> 04:04:55,280 OF LEAKING, RIGHT, WITHOUT ANY 4698 04:04:55,280 --> 04:04:57,960 TRAINING AND IN A FREELY MOVING 4699 04:04:57,960 --> 04:04:59,600 ANIMALS FOR THE FIRST TIME. 4700 04:04:59,600 --> 04:05:01,880 SO, NOW WE'RE STARTING TO THINK 4701 04:05:01,880 --> 04:05:03,520 MAYBE, COULD IT BE IF THESE WERE 4702 04:05:03,520 --> 04:05:05,160 SELECTED THROUGH OUT THE 4703 04:05:05,160 --> 04:05:07,440 EVOLUTION, TO PRODUCE A CERTAIN 4704 04:05:07,440 --> 04:05:09,320 BEHAVIORAL PATTERN THEY ALSO, 4705 04:05:09,320 --> 04:05:10,920 YOU KNOW, THROUGH COLLATERAL, 4706 04:05:10,920 --> 04:05:15,920 THESE NEURONS AS THEY DESCEND 4707 04:05:15,920 --> 04:05:20,560 THEY DON'T JUST PROTECT TO ONE 4708 04:05:20,560 --> 04:05:22,560 SPECIFIC TYPE MANY OF SO THESE 4709 04:05:22,560 --> 04:05:25,320 WOULD BE, SUPER EXCITING IF 4710 04:05:25,320 --> 04:05:27,520 THERE WERE COORDINATED MODULES 4711 04:05:27,520 --> 04:05:30,000 THAT ARE NOT ONLY FOR ADVERSE 4712 04:05:30,000 --> 04:05:32,480 BEHAVIOR BUT FOR ADVERSE 4713 04:05:32,480 --> 04:05:35,400 BEHAVIOR AND -- THE ENTIRE 4714 04:05:35,400 --> 04:05:37,200 PHYSIOLOGICAL RESPONSE WHICH IS 4715 04:05:37,200 --> 04:05:41,000 NOT THE ONLY MUSCULAR. 4716 04:05:41,000 --> 04:05:42,440 >>IT'S KNOWN FOR EXERCISE, 4717 04:05:42,440 --> 04:05:43,320 ISN'T IT. 4718 04:05:43,320 --> 04:05:44,840 OF COURSE IT'S TRUE AND ANIMALS 4719 04:05:44,840 --> 04:05:49,640 START TO RUN THAT IT'S GOING TO 4720 04:05:49,640 --> 04:05:51,080 REGULATE IT'S HEART RATE AND 4721 04:05:51,080 --> 04:05:53,520 BLOOD PRESSURES IN WAYS THAT ARE 4722 04:05:53,520 --> 04:05:53,840 COORDINATED. 4723 04:05:53,840 --> 04:05:54,920 I DON'T KNOW WHETHER PEOPLE IN 4724 04:05:54,920 --> 04:05:56,720 THE ROOM WHETHER NO WHETHER IT 4725 04:05:56,720 --> 04:05:59,040 HAS COLLATERALS THAT ARE CONTROL 4726 04:05:59,040 --> 04:05:59,200 TAG? 4727 04:05:59,200 --> 04:06:04,840 ING THAT.>>THIS COULD BE A GOOO 4728 04:06:04,840 --> 04:06:05,680 START A DISCUSSION. 4729 04:06:05,680 --> 04:06:09,400 IMAGINE IF YOU START MUSCULAR -- 4730 04:06:09,400 --> 04:06:12,400 I MEAN, RUNNING AND ACTIVATING 4731 04:06:12,400 --> 04:06:15,680 YOUR MUSCLES, DOES YOUR HEART 4732 04:06:15,680 --> 04:06:18,200 START TO PREPARE FOR THAT IN 4733 04:06:18,200 --> 04:06:18,560 ANTICIPATION? 4734 04:06:18,560 --> 04:06:20,920 I MEAN, CERTAINLY THE LUNGS WITH 4735 04:06:20,920 --> 04:06:22,600 NO RESPIRATION STARTS. 4736 04:06:22,600 --> 04:06:24,680 >>RESPIRATION STARTS FIRST SO 4737 04:06:24,680 --> 04:06:27,440 IT GOES UP DUE TO VAGAL 4738 04:06:27,440 --> 04:06:28,600 INTERFERENCE AND CARDIAC 4739 04:06:28,600 --> 04:06:30,360 CONTROLS COMES ON LATER SO YOU 4740 04:06:30,360 --> 04:06:30,720 GET A LAG. 4741 04:06:30,720 --> 04:06:33,720 BUT YOU ALSO HAVE CENTRAL 4742 04:06:33,720 --> 04:06:34,920 DESCENDING CONTROLS. 4743 04:06:34,920 --> 04:06:38,560 >>AND IF IT COORDINATED IN THE 4744 04:06:38,560 --> 04:06:40,960 SENSE THAT IT STIMULATES ONE 4745 04:06:40,960 --> 04:06:41,160 THING. 4746 04:06:41,160 --> 04:06:43,200 >>YOU GET THAT IMMEDIATE UP 4747 04:06:43,200 --> 04:06:47,320 REGULATION RESPIRATION AND THEN 4748 04:06:47,320 --> 04:06:49,720 YOU GRADUALLY GET REFLEX AS YOU 4749 04:06:49,720 --> 04:06:51,200 PRODUCE METABOLITES AND YOU GET 4750 04:06:51,200 --> 04:06:53,200 TIE POINT WHERE YOU LEVEL OFF ON 4751 04:06:53,200 --> 04:06:54,080 YOUR WORKLOAD. 4752 04:06:54,080 --> 04:06:55,240 THE IMMEDIATE CHANGES ARE 4753 04:06:55,240 --> 04:06:55,720 CENTRALLY DRIVEN. 4754 04:06:55,720 --> 04:06:57,280 >>THAT'S COOL. 4755 04:06:57,280 --> 04:06:59,840 WE START A POPULATIONS IN THE 4756 04:06:59,840 --> 04:07:03,320 BRAIN STEM AND IT CAN BE IN USED 4757 04:07:03,320 --> 04:07:10,320 STIMULATION VERY QUICKLY AND 4758 04:07:10,320 --> 04:07:14,400 IT'S INTERESTING BEFORE OR AND 4759 04:07:14,400 --> 04:07:15,920 AND IF YOU HAVE THESE, YEAH. 4760 04:07:15,920 --> 04:07:18,720 >>YOU ARE A URF HERE? 4761 04:07:18,720 --> 04:07:19,640 >> 4762 04:07:19,640 --> 04:07:20,040 [LAUGHTER] 4763 04:07:20,040 --> 04:07:26,640 >>I WOULD SIT DOWN. 4764 04:07:26,640 --> 04:07:27,880 >>WE HAVE A COUPLE OF QUESTIONS 4765 04:07:27,880 --> 04:07:30,360 AND THE FIRST Dr. FOR Dr. 4766 04:07:30,360 --> 04:07:30,640 ANDERMANN. 4767 04:07:30,640 --> 04:07:32,480 I HAVE A COUPLE OF QUESTIONS FOR 4768 04:07:32,480 --> 04:07:34,800 Dr. ANDERMANN. 4769 04:07:34,800 --> 04:07:36,560 HAVE YOU INVESTIGATED THE 4770 04:07:36,560 --> 04:07:38,120 QUESTION UNDERLINE PATHOLOGICAL 4771 04:07:38,120 --> 04:07:40,000 EATING DISORDERS AND ALSO WHAT 4772 04:07:40,000 --> 04:07:41,200 FEATURES IN THE SIGNAL DID YOU 4773 04:07:41,200 --> 04:07:44,360 USE TO UNDERSTAND WHETHER THE 4774 04:07:44,360 --> 04:07:46,760 ACTIVITIES INDICATED FOOD 4775 04:07:46,760 --> 04:07:48,160 DEFICIT VERSUS FOOD SURPLUS, 4776 04:07:48,160 --> 04:07:50,800 IT'S A VERY INTERESTING TALK. 4777 04:07:50,800 --> 04:07:51,920 THANK YOU. 4778 04:07:51,920 --> 04:07:53,600 >>THANK YOU FOR THE QUESTION 4779 04:07:53,600 --> 04:07:55,840 AND THIS IS THE SECOND ONE BUT 4780 04:07:55,840 --> 04:07:57,520 THE FIRST QUESTION WAS REGARDS 4781 04:07:57,520 --> 04:08:01,000 TO THE INSULAR CORTEX IN EATING 4782 04:08:01,000 --> 04:08:01,920 DISORDERS. 4783 04:08:01,920 --> 04:08:04,760 ACTUALLY, THE MOST INTERESTING 4784 04:08:04,760 --> 04:08:06,080 LITERATURE THAT IS QUITE 4785 04:08:06,080 --> 04:08:09,160 COMPELLING TO ME IN HUMANS WITH 4786 04:08:09,160 --> 04:08:11,080 LAUCHANCE OR STROKES TO THE 4787 04:08:11,080 --> 04:08:12,880 CORTEX ACTUAL LOW HAD TO DO WITH 4788 04:08:12,880 --> 04:08:15,280 THE FACT THAT IT'S EASIER TO 4789 04:08:15,280 --> 04:08:17,880 QUIT SMOKING AND TO QUIT OTHER 4790 04:08:17,880 --> 04:08:19,360 ADDICTIONS IN THAT CONTEXT AND 4791 04:08:19,360 --> 04:08:21,840 SO I THINK IN SOME WAYS, THIS IS 4792 04:08:21,840 --> 04:08:23,160 CONSISTENT WITH WHAT I WAS 4793 04:08:23,160 --> 04:08:26,600 PROPOSING IN THE TALK WHICH IS 4794 04:08:26,600 --> 04:08:28,360 THAT THE INSULAR CORTEX MAY BE 4795 04:08:28,360 --> 04:08:31,480 PART OF A NETWORK THAT 4796 04:08:31,480 --> 04:08:32,440 INTEGRATES THE GOOD FEELINGS AND 4797 04:08:32,440 --> 04:08:34,480 THE BAD FEELINGS OF TAKING 4798 04:08:34,480 --> 04:08:40,280 INACTION AND IF THERE'S SOMEWAY 4799 04:08:40,280 --> 04:08:42,760 OF PER SEVER ANSON MOTOR BEHAVE 4800 04:08:42,760 --> 04:08:43,920 YEARS THAT MAINTAIN A STATE SUCH 4801 04:08:43,920 --> 04:08:46,440 AS A STATE OF NICOTINE 4802 04:08:46,440 --> 04:08:48,080 DEPENDENCE, DESPITE THE TASTE OF 4803 04:08:48,080 --> 04:08:49,640 NICOTINE AND SO ON THAT MIGHT 4804 04:08:49,640 --> 04:08:52,160 REQUIRE THE CORTEX TO KIND OF 4805 04:08:52,160 --> 04:08:53,400 EXERT ITS CONTROL AND THAT WHEN 4806 04:08:53,400 --> 04:08:56,600 YOU TAKEAWAY THE INSULAR CORTEX, 4807 04:08:56,600 --> 04:08:58,080 IT'S EASIER TO QUIT THE SMOKING 4808 04:08:58,080 --> 04:08:59,960 BECAUSE YOU DON'T HAVE THE SORT 4809 04:08:59,960 --> 04:09:02,640 OF WANTING TO PERSIST. 4810 04:09:02,640 --> 04:09:07,440 DIDN'T CATCH THE SECOND 4811 04:09:07,440 --> 04:09:07,680 QUESTION. 4812 04:09:07,680 --> 04:09:08,360 >>THAT'S GOOD. 4813 04:09:08,360 --> 04:09:09,800 THANK YOU. 4814 04:09:09,800 --> 04:09:19,320 >>THE NEXT QUESTION FOR Dr. 4815 04:09:19,320 --> 04:09:20,560 HEIKE MUENZBERG-GRUENING. 4816 04:09:20,560 --> 04:09:24,560 CAN YOU CHANGE IT TO FAT TISSUE 4817 04:09:24,560 --> 04:09:25,520 IN TH DRIVEN. 4818 04:09:25,520 --> 04:09:29,200 HOW DO YOU ELIMINATE THE VAGAL 4819 04:09:29,200 --> 04:09:32,000 AND SPINAL TH POSITIVE SENSORY 4820 04:09:32,000 --> 04:09:32,800 NEURONS? 4821 04:09:32,800 --> 04:09:37,680 HAVE YOU TRIED LOCAL AV 4822 04:09:37,680 --> 04:09:43,840 DELIVERY, HM3DQ? 4823 04:09:43,840 --> 04:09:47,920 >>THE TH3 MOUSE MODEL WE WERE 4824 04:09:47,920 --> 04:09:50,280 USING SAUL SYMPATHETIC AND IT'S 4825 04:09:50,280 --> 04:09:55,720 TRUE THAT VAGAL IS TO IT'S 4826 04:09:55,720 --> 04:09:59,240 EXPRESSED IN THE VAGAL AND SO WE 4827 04:09:59,240 --> 04:10:00,800 DON'T DISTINGUISH THAT SO WE 4828 04:10:00,800 --> 04:10:02,840 WANT AID SYSTEM WHERE WE HAVE A 4829 04:10:02,840 --> 04:10:05,240 MORE BROAD STIMULATION OF 4830 04:10:05,240 --> 04:10:08,760 SYMPATHETIC AND COULD WE GET A 4831 04:10:08,760 --> 04:10:09,720 SIMULATION OF TEMPERATURES 4832 04:10:09,720 --> 04:10:11,200 BECAUSE OF A SURPRISING TO US 4833 04:10:11,200 --> 04:10:15,880 THAT THAT IS THE THAT SHOULD 4834 04:10:15,880 --> 04:10:17,160 INCREASE FROM THE TEMPERATURE 4835 04:10:17,160 --> 04:10:18,640 AND IT DOES NOT. 4836 04:10:18,640 --> 04:10:20,240 SO WHAT IT SHOWS US WAS 4837 04:10:20,240 --> 04:10:23,440 BASICALLY THAT YEAH, IT'S 4838 04:10:23,440 --> 04:10:25,680 POSSIBLE TO GET ACTIVATED 4839 04:10:25,680 --> 04:10:26,880 TEMPERATURES IS JUST NOT 4840 04:10:26,880 --> 04:10:31,400 SUFFICIENT IF YOU ONLY ARE 4841 04:10:31,400 --> 04:10:33,080 DRIVER TO BRONZE FED. 4842 04:10:33,080 --> 04:10:34,760 >>Dr. COSTA, THE NEXT 4843 04:10:34,760 --> 04:10:36,160 QUESTION IS FOR YOU. 4844 04:10:36,160 --> 04:10:38,800 DO YOU SEE DRG NEURONS THAT 4845 04:10:38,800 --> 04:10:43,040 PROJECT DIRECTLY INTO THE 4846 04:10:43,040 --> 04:10:43,520 PANCREAS? 4847 04:10:43,520 --> 04:10:52,840 >>SO, WE HAVE NOT EXPLORED SO 4848 04:10:52,840 --> 04:10:56,600 MUCH OF THE SENSORY SIDE. 4849 04:10:56,600 --> 04:10:58,920 WE KNOW THE STOMACH, RIGHT. 4850 04:10:58,920 --> 04:11:00,320 I WOULD IMAGINE THAT YES. 4851 04:11:00,320 --> 04:11:01,600 I DON'T KNOW IF IT'S THE SAME 4852 04:11:01,600 --> 04:11:04,680 ONE OF THE STOMACH WE KNOW. 4853 04:11:04,680 --> 04:11:06,800 ONE INTERESTING THING SO ON THE 4854 04:11:06,800 --> 04:11:08,960 DRG SIDE ON THE SENSORY SIDE, WE 4855 04:11:08,960 --> 04:11:10,840 DON'T HAVE AS MUCH MAPPING. 4856 04:11:10,840 --> 04:11:12,400 ONE INTERESTING THING I MEAN, 4857 04:11:12,400 --> 04:11:15,840 BECAUSE WE TALK ABOUT 4858 04:11:15,840 --> 04:11:17,760 SYMPATHETIC AND HERE AS TWO 4859 04:11:17,760 --> 04:11:20,800 DIFFERENT SYSTEMS BUT FOR 4860 04:11:20,800 --> 04:11:24,000 EXAMPLE, TO THE GANG LEANNE AND 4861 04:11:24,000 --> 04:11:26,480 THAT THE SPLEEN DOES NOT SEEM TO 4862 04:11:26,480 --> 04:11:29,360 HAVE DIRECT VAGAL INNOVATION AND 4863 04:11:29,360 --> 04:11:33,480 THERE IS INNOVATION OF THE 4864 04:11:33,480 --> 04:11:36,080 GANGLIA BY THE VAGUS WHICH IS 4865 04:11:36,080 --> 04:11:39,760 SUPPOSEDLY A SYMPATHETIC SYSTEM 4866 04:11:39,760 --> 04:11:45,600 SO ON THE PANCREAS, YOU GET BOTH 4867 04:11:45,600 --> 04:11:49,000 SYMPATHETIC AND SO YOU KNOW, 4868 04:11:49,000 --> 04:11:50,440 MAYBE INSTEAD OF SYSTEMS THESE 4869 04:11:50,440 --> 04:11:52,040 ARE NEURONS AND WE HAVE A 4870 04:11:52,040 --> 04:11:55,920 CERTAIN TYPE OF NEURO 4871 04:11:55,920 --> 04:11:56,600 TRANSMITTERS AND EXPRESSIONS 4872 04:11:56,600 --> 04:11:58,360 THAT ARE COORDINATED FOR 4873 04:11:58,360 --> 04:12:03,320 RECEIVING AND AGAIN I THINK THAT 4874 04:12:03,320 --> 04:12:08,160 NOT DRG BUT THE DORRAL MOTOR 4875 04:12:08,160 --> 04:12:15,800 VAGUS NUCHAVING NUCLEUS. 4876 04:12:15,800 --> 04:12:17,080 I DON'T KNOW IF YOU HAVE THE 4877 04:12:17,080 --> 04:12:17,400 DATA HERE. 4878 04:12:17,400 --> 04:12:22,640 >>D RG INNERVATING THE PANCREAS 4879 04:12:22,640 --> 04:12:23,520 IT'S CLEAR. 4880 04:12:23,520 --> 04:12:24,520 ONE INTERESTING THING ABOUT SOME 4881 04:12:24,520 --> 04:12:27,160 OF THIS INTERNAL ORGANS, 4882 04:12:27,160 --> 04:12:28,720 ESPECIALLY THE PANCREAS IS 4883 04:12:28,720 --> 04:12:30,640 SOMETHING IN HUMANS CALLED 4884 04:12:30,640 --> 04:12:32,800 REFERRAL PAIN WHICH IS THAT 4885 04:12:32,800 --> 04:12:35,600 PEOPLE WITH SAY PROBLEMS IN THE 4886 04:12:35,600 --> 04:12:37,520 PANCREAS, THEY PERCEIVED PAIN IN 4887 04:12:37,520 --> 04:12:39,440 DIFFERENT AREAS OF THE BODY AND 4888 04:12:39,440 --> 04:12:41,480 SO THE WAY THAT THE ARRANGEMENTS 4889 04:12:41,480 --> 04:12:44,760 OF THE CIRCUITRY USED IS UNCLEAR 4890 04:12:44,760 --> 04:12:53,880 BUT THERE'S INNER HA PANCREATIC 4891 04:12:53,880 --> 04:12:56,080 PAIN IN CANCER IS A PROBLEM. 4892 04:12:56,080 --> 04:12:59,440 >>IN THE SPLEEN, WHEN THERE'S 4893 04:12:59,440 --> 04:13:01,400 THE CON TRACKTURE MANY OF YOU 4894 04:13:01,400 --> 04:13:02,480 PROBABLY HAVE NOTICED. 4895 04:13:02,480 --> 04:13:04,480 >>YEAH, EXACTLY. 4896 04:13:04,480 --> 04:13:09,760 AND IT'S ALSO TRUE THAT MANY 4897 04:13:09,760 --> 04:13:13,600 TERMINALS INNERVATE CELIAC SOME 4898 04:13:13,600 --> 04:13:15,760 NEURONS COME FROM THE INTESTINE 4899 04:13:15,760 --> 04:13:22,280 AND THERE'S SOME VAGAL WITH THE 4900 04:13:22,280 --> 04:13:23,280 NEURONS OF THE SPINAL CORD SO 4901 04:13:23,280 --> 04:13:26,000 IT'S A VERY COMPLICATED GAME FOR 4902 04:13:26,000 --> 04:13:26,400 SURE. 4903 04:13:26,400 --> 04:13:27,520 IT'S VERY INTERESTING. 4904 04:13:27,520 --> 04:13:30,840 >>WELL, THAT, WE'LL END THIS 4905 04:13:30,840 --> 04:13:31,040 SESSION. 4906 04:13:31,040 --> 04:13:32,080 THANK YOU ALL VERY MUCH AND MOVE 4907 04:13:32,080 --> 04:13:38,400 ON TO CLOSE REMARKS BY Dr. 4908 04:13:38,400 --> 04:13:38,680 VALENTINO. 4909 04:13:38,680 --> 04:13:40,240 >>THANK YOU, IT'S A DIFFICULT 4910 04:13:40,240 --> 04:13:40,480 TASK. 4911 04:13:40,480 --> 04:13:46,320 I HAVE TO SAY THAT THIS WAS A 4912 04:13:46,320 --> 04:13:48,160 VERY ENTA ELECTRIC ACTUALLY 4913 04:13:48,160 --> 04:13:49,200 ENERGIZING MEETING AND IT WAS 4914 04:13:49,200 --> 04:13:51,720 JUST A LOT OF FUN AND I FIRST 4915 04:13:51,720 --> 04:13:53,360 WANT TO THANK EVERYONE TODAY. 4916 04:13:53,360 --> 04:13:54,800 I WANT TO THANK ALL OF THE 4917 04:13:54,800 --> 04:13:56,600 SPEAKERS, ALL OF THE ORGANIZERS 4918 04:13:56,600 --> 04:13:58,240 AND THOSE WHO WORKED WITH THE 4919 04:13:58,240 --> 04:13:59,560 LOGISTICS EVEN THOUGH WE HAD 4920 04:13:59,560 --> 04:14:01,040 GLITCHES, WE'RE ENDING ON TIME 4921 04:14:01,040 --> 04:14:02,520 AND DOING GREAT. 4922 04:14:02,520 --> 04:14:05,640 AND I PARTICULARLY WANT TO 4923 04:14:05,640 --> 04:14:09,080 ACKNOWLEDGE, WHEN, FOR RALLY 4924 04:14:09,080 --> 04:14:11,000 TAKING ON THIS VISION AND YOU 4925 04:14:11,000 --> 04:14:13,640 KNOW, AND YOU CAN HAVE A 4926 04:14:13,640 --> 04:14:14,720 PARTICULAR VISION BUT AN 4927 04:14:14,720 --> 04:14:16,600 IMPORTANT THING IS FINDING THE 4928 04:14:16,600 --> 04:14:18,040 RIGHT TIME TO PRESENT IT AND I 4929 04:14:18,040 --> 04:14:20,360 THINK THAT'S ONE OF THE THINGS 4930 04:14:20,360 --> 04:14:22,040 THAT SHE DID. 4931 04:14:22,040 --> 04:14:24,520 SHE RECOGNIZED THAT THE TIMING 4932 04:14:24,520 --> 04:14:27,000 WAS RIGHT TO DEVELOP AND PROMOTE 4933 04:14:27,000 --> 04:14:31,320 THIS INITIATIVE AND I THINK WE 4934 04:14:31,320 --> 04:14:33,560 HAD 2019, A COUPLE YEARS AGO, WE 4935 04:14:33,560 --> 04:14:35,080 HAD THE FIRST MEETING AND WE 4936 04:14:35,080 --> 04:14:36,280 TALKED ABOUT THE CHALLENGES AND 4937 04:14:36,280 --> 04:14:39,680 IT WAS VERY EXCITING AND I THINK 4938 04:14:39,680 --> 04:14:42,880 PRIOR TO THAT, I KNOW A LOT OF 4939 04:14:42,880 --> 04:14:46,080 IS IS THAT KIND OF WORKED ON THE 4940 04:14:46,080 --> 04:14:48,320 BRAIN ADVISER A INTERACTIONS 4941 04:14:48,320 --> 04:14:49,880 FELT LIKE THE WORK WAS ON THE 4942 04:14:49,880 --> 04:14:50,720 FRINGE AND IT WAS FALLING 4943 04:14:50,720 --> 04:14:52,120 BETWEEN THE CRACKS OF 4944 04:14:52,120 --> 04:14:52,400 INSTITUTES. 4945 04:14:52,400 --> 04:14:59,480 I KNOW THAT I FELT THAT WAY. 4946 04:14:59,480 --> 04:15:03,200 AND TWO YEARS AFTER THIS MEETING 4947 04:15:03,200 --> 04:15:08,440 OUR KEYNOTE SPEAKER WAS A NOBLE 4948 04:15:08,440 --> 04:15:12,640 LAUREATE AND THAT'S REAL FIFTH Y 4949 04:15:12,640 --> 04:15:13,000 IMPORTANT. 4950 04:15:13,000 --> 04:15:16,280 WE DISCUSSED WHEN PRESENTED 4951 04:15:16,280 --> 04:15:19,760 EARLIER HOW THIS INITIATIVE 4952 04:15:19,760 --> 04:15:20,840 LANDS BETWEEN BRAIN AND LINKS 4953 04:15:20,840 --> 04:15:23,800 BETWEEN THE BRAIN INITIATIVE AND 4954 04:15:23,800 --> 04:15:28,440 THE SPARC INITIATIVE 4955 04:15:28,440 --> 04:15:29,600 INNERRIZATION OF PERIPHERAL 4956 04:15:29,600 --> 04:15:30,760 ORGANS SO IT'S TRUE WE'RE 4957 04:15:30,760 --> 04:15:33,640 BEGINNING TO IDENTIFY RECIPROCAL 4958 04:15:33,640 --> 04:15:37,800 COMMUNICATIONS, WAYS OF 4959 04:15:37,800 --> 04:15:38,760 RECIPROCAL COMMUNICATION BETWEEN 4960 04:15:38,760 --> 04:15:41,440 THE BRYN AND PERIPHERAL ORGANS. 4961 04:15:41,440 --> 04:15:44,600 THIS IS REALLY A STORY OF 4962 04:15:44,600 --> 04:15:45,920 MULTI-SYSTEM INTEGRATION AND HOW 4963 04:15:45,920 --> 04:15:54,920 DOES THE ADVIS -- HOW IS IT HARD 4964 04:15:54,920 --> 04:15:57,800 WITH ALL THE OTHER SOUNDS? 4965 04:15:57,800 --> 04:15:59,320 UNDERSTANDING THIS IS REALLY 4966 04:15:59,320 --> 04:16:02,960 INFORMS US OF HOW MULTI SYSTEMS 4967 04:16:02,960 --> 04:16:04,760 ORGANISMS, WE CAN REALLY BEGIN 4968 04:16:04,760 --> 04:16:10,080 TO NAVIGATE OUR UNIVERSE OR OUR 4969 04:16:10,080 --> 04:16:11,600 ENVIRONMENT AND ALSO INFORMS US 4970 04:16:11,600 --> 04:16:14,880 HOW PATHOLOGY CAN PRESENT AS CO 4971 04:16:14,880 --> 04:16:20,640 MORBID CENTRAL AND PERIPHERAL 4972 04:16:20,640 --> 04:16:22,080 FEATURES, WE'RE LEARNING FROM 4973 04:16:22,080 --> 04:16:24,240 THE BRAIN INITIATIVE AND SPARC 4974 04:16:24,240 --> 04:16:26,080 THE IMPORTANCE OF TECHNOLOGY AND 4975 04:16:26,080 --> 04:16:30,200 HOW THIS ADVANCES KNOWLEDGE AND 4976 04:16:30,200 --> 04:16:33,520 OUR KEYNOTE SPEAKER TODAY, 4977 04:16:33,520 --> 04:16:35,680 REALLY REINFORCED THIS IDEA AND 4978 04:16:35,680 --> 04:16:39,320 IN THE INTERCEPTION PROGRAM. 4979 04:16:39,320 --> 04:16:41,560 SHE ALSO PRESENTED AND SHOWED 4980 04:16:41,560 --> 04:16:44,440 THERE WERE UNIQUE CHALLENGES IN 4981 04:16:44,440 --> 04:16:46,600 ACCESSING TISSUE AND VISUALIZING 4982 04:16:46,600 --> 04:16:49,360 AND RECORDING AND MANIPULATING 4983 04:16:49,360 --> 04:16:50,840 AND I THOUGHT THAT WAS VERY 4984 04:16:50,840 --> 04:16:54,680 IMPORTANT AND THE NEED TO 4985 04:16:54,680 --> 04:16:57,120 INCORPORATE BIO ENGINEERING, NEW 4986 04:16:57,120 --> 04:16:58,880 BIO ENGINEERING APPROACHES TO 4987 04:16:58,880 --> 04:17:03,760 OVERCOME THE CHALLENGES. 4988 04:17:03,760 --> 04:17:05,040 ALL THE SCIENCE PREVENTED NEW 4989 04:17:05,040 --> 04:17:06,560 KNOWLEDGE AND OPENED UP, AS GOOD 4990 04:17:06,560 --> 04:17:08,960 RESEARCH DOES, IT OPENS UP NEW 4991 04:17:08,960 --> 04:17:14,000 QUESTIONS SOFI.WE LEARNED THE UF 4992 04:17:14,000 --> 04:17:15,200 MULTI-PRONGED APPROACH AND HOW 4993 04:17:15,200 --> 04:17:16,480 THE BRAIN REGULATES THE STOMACH 4994 04:17:16,480 --> 04:17:18,160 AND THE NEED TO UNDERSTAND THE 4995 04:17:18,160 --> 04:17:22,480 INNER PLAY BETWEEN VAGAL AND 4996 04:17:22,480 --> 04:17:24,680 SPINAL NETWORKS AND DISPLAYING 4997 04:17:24,680 --> 04:17:28,600 GASTRO INFORMATION TO THE BRAIN. 4998 04:17:28,600 --> 04:17:32,960 THE RECOGNIZE T -- THIS CAN EVEG 4999 04:17:32,960 --> 04:17:35,320 BEHAVIOR IS FASCINATING AND IT'S 5000 04:17:35,320 --> 04:17:36,640 IMPORTANT TO UNDERSTAND HOW AND 5001 04:17:36,640 --> 04:17:38,160 WHEN THIS WOULD BE ENGAGE AND 5002 04:17:38,160 --> 04:17:43,560 HOW IT INTERACTS WITH HAVINGEL 5003 04:17:43,560 --> 04:17:47,280 OUT PUTS. 5004 04:17:47,280 --> 04:17:49,440 IT REVEALED CIRCUITS AND REFLEX 5005 04:17:49,440 --> 04:17:50,720 RESPONSES AND RELATED TO 5006 04:17:50,720 --> 04:17:53,520 BREATHING AND RELATED TO CARDIAC 5007 04:17:53,520 --> 04:17:56,960 FUNCTION AND RELATE TODAY 5008 04:17:56,960 --> 04:17:57,640 METABOLISM AND THIS IS 5009 04:17:57,640 --> 04:17:59,560 INFORMATION THAT IS CRITICAL TO 5010 04:17:59,560 --> 04:18:00,760 UNDERSTANDING THE BIGGER 5011 04:18:00,760 --> 04:18:02,400 QUESTION OF HOW ARE THESE 5012 04:18:02,400 --> 04:18:05,240 REFLEXES LINKED TO COGNITIVE AND 5013 04:18:05,240 --> 04:18:05,840 EMOTIONAL FUNCTION. 5014 04:18:05,840 --> 04:18:07,560 HOW DO THEY INTERACT WITH THESE 5015 04:18:07,560 --> 04:18:08,040 FUNCTIONS? 5016 04:18:08,040 --> 04:18:11,320 I ONLY HEARD THE WORD AMYGDALA 5017 04:18:11,320 --> 04:18:12,400 ONCE TODAY I WAS SHOCKED AND IT 5018 04:18:12,400 --> 04:18:16,880 WAS IN PASSING. 5019 04:18:16,880 --> 04:18:17,720 HOW DOES THAT HAPPEN? 5020 04:18:17,720 --> 04:18:19,600 I THOUGHT IT WAS GOOD BECAUSE IT 5021 04:18:19,600 --> 04:18:22,560 MEANS THINGS ARE CHANGING AND 5022 04:18:22,560 --> 04:18:25,240 OTHER THINGS ARE COMING INTO 5023 04:18:25,240 --> 04:18:25,600 PLAY. 5024 04:18:25,600 --> 04:18:28,880 SO TO ME, THE STRESS RESPONSES 5025 04:18:28,880 --> 04:18:34,480 ARE A BEAUTIFUL EXAMPLE OF HOW 5026 04:18:34,480 --> 04:18:36,480 ALL OF THESE PERIPHERAL 5027 04:18:36,480 --> 04:18:40,760 RESPONSES, BREATHING, CARDIAC 5028 04:18:40,760 --> 04:18:41,920 CHANGES, GASTROINTESTINAL 5029 04:18:41,920 --> 04:18:43,240 CHANGES, CHANGES IN BLADDER 5030 04:18:43,240 --> 04:18:45,360 FUNCTION AND IMMUNE FUNCTION AND 5031 04:18:45,360 --> 04:18:47,520 METABOLISM, THEY ALL HAVE TO BE 5032 04:18:47,520 --> 04:18:49,960 COORDINATED AND VERY PRECISE 5033 04:18:49,960 --> 04:18:52,480 FASHION WITH BEHAVIOR AND 5034 04:18:52,480 --> 04:18:53,920 COGNITIVE FUNCTION AND TO BE 5035 04:18:53,920 --> 04:18:56,040 ABLE TO ADAPT TO 5036 04:18:56,040 --> 04:18:59,400 LIFE-THREATENING ST STIMULUS AND 5037 04:18:59,400 --> 04:19:02,480 ANY DISREGULATION OF THAT 5038 04:19:02,480 --> 04:19:04,160 COORDINATION RESULTS IN STRESS 5039 04:19:04,160 --> 04:19:06,640 RELATED DISORDERS AND STRESS 5040 04:19:06,640 --> 04:19:09,320 RELATED DISEASES SO I THINK WHAT 5041 04:19:09,320 --> 04:19:11,400 WE'RE TRYING TO UNDERSTAND HERE 5042 04:19:11,400 --> 04:19:13,000 IS HOW, THAT'S JUST AN EXAMPLE 5043 04:19:13,000 --> 04:19:14,720 TO ME OF HOW THINGS ARE KIND OF 5044 04:19:14,720 --> 04:19:19,120 SUPPOSED TO WORK TOGETHER AND I 5045 04:19:19,120 --> 04:19:21,560 THINK WHAT I LIKE ABOUT THIS 5046 04:19:21,560 --> 04:19:22,560 INITIATIVE AND ALL THE RESEARCH 5047 04:19:22,560 --> 04:19:24,480 THAT YOU ALL ARE DOING IS IT'S 5048 04:19:24,480 --> 04:19:27,040 GOING TO BEGIN TO ANSWER THOSE 5049 04:19:27,040 --> 04:19:29,520 QUESTIONS AND TO REALLY, AT THE 5050 04:19:29,520 --> 04:19:29,880 END. 5051 04:19:29,880 --> 04:19:33,320 GIVE US A PICTURE OF HOW THIS 5052 04:19:33,320 --> 04:19:35,840 WORKS AND OF THIS COORDINATION 5053 04:19:35,840 --> 04:19:38,400 THAT REALLY ALLOWS US TO 5054 04:19:38,400 --> 04:19:38,760 SURVIVE. 5055 04:19:38,760 --> 04:19:40,520 SO I EXPECT THAT WE'LL GET EVEN 5056 04:19:40,520 --> 04:19:42,440 MORE ADVANCED TECHNOLOGIES THAT 5057 04:19:42,440 --> 04:19:44,160 ALLOW HIGHER RESOLUTION ACCESS 5058 04:19:44,160 --> 04:19:46,440 AND MANIPULATION AND GET US 5059 04:19:46,440 --> 04:19:49,640 CLOSER TO THIS BIG PICTURE. 5060 04:19:49,640 --> 04:19:50,880 THANK YOU FOR COMING AND I'M 5061 04:19:50,880 --> 04:19:53,720 LOOKING FORWARD TO TOMORROW. 5062 04:19:53,720 --> 04:20:03,920 [APPLAUSE]