--HERE AT THE NIH.
AND I AM VERY EXCITED TO
INTRODUCE TO YOU TODAY'S SPEAKER
WHO'S DR. ERICHSPAY JARVIS WHO
IS A WORLD RENOWNED EXPERT OF
GENOMICS AND MOLECAR MECHANISM
UNDERLYING THE LEARNING OF FOCAL
LEARNING AND COMPLEX BEHAVIORS.
FIRST WE HAVE SOME HOUSEKEEPING.
FOR THOSE WHO ARE WATCHING
REMOTELY.
WE ENCOURAGE YOU TO PARTICIPATE
IN TODAY'S PRESENTATION BY
OFFERING QUESTIONS USING THE
SEND LIVE FEEDBACK BUTTON ON THE
VIDEOCAST.
IF YOU PUT IN YOUR NAME AND
QUESTION AT ANY POINT DURING THE
PRESENTATION, WE WILL INSURE WE
CAN GET TO THAT TOWARDS THE END
OF THE LECTURE.
IF YOU ARE IN THE AUDITORIUM
THERE ARE MICROPHONES IN EITHER
SIDE OF THE AISLES ON THE LEFT
OR RIGHT THAT I WILL UTILIZE.
AND THEN FINALLY, WE ARE ALSO
OFFERING CONTINUING MEDICAL
EDUCATION CREDITS FOR THIS
PRESENTATION, THE CME CODE IS UP
THERE BUT FOR THOSE ONLEAN, IT'S
JUST 501, 01.
I WILL REPEAT THAT 1 MORE TIME
50101.
I WILL WAIT TO HEAR BINGO!
[LAUGHTER]
SO THIS IS NOT JUST ANOTHER TALK
ON THE WALS CALENDAR.
HE ALSO GAVE THE LECTURE
ESTABLISHED IN 2011 AND IT
RECOGNIZES NUREMBERG, CODE,
ALTHOUGH DR. NUREMBERG DIED, BUT
IT INCLUDED NEW O GENETICS FIEWR
O SCIENCE AND NEURODEVELOPMENT
AND THE BOX GENES AND ARE
PARTICULARLY RELEVANT TO OUR
SPEAKER TODAY.
AND IF YOU VBT ALREADY SEEN IT,
I ENCOURAGE TO YOU TAKE A
ELECTRIC AT THE WONDERFUL
EXHIBIT OF DR. NUREMBERG'S WORK
WHICH JUST OUTSIDE THE
AUDITORIUM HERE.
I AM ALSO TOLD THAT THE DOCTOR'S
FAMILY MAY BE ONLINE AND IF
THAT'S THE CASE I WANT TO OFFER
THEM A VERY SPECIAL AND WARM
WELCOME.
OKAY, ON TO OUR SPEAKER TODAY.
SO ERICH JARVIS IS THE DIRECTOR
OF THE FIELD RESEARCH CENTER FOR
ETHOLOGY AND [INDISCERNIBLE] AT
GENOME LAB AT ROCKEFELLER.
DR. JARVIS' WORK USES SONG BIRDS
AND OTHER SPECIES TO STUDY THE
TO LEC BAR AND GENETIC
MECHANISMS THAT UNDERLIE VOCAL
LEARNING INCLUDING HOW HUMANS
LEARN SPOKEN LANGUAGE, AND HE'S
INTERESTED IN HOW THEIR BRAINS
AND OURS HAVE EVOLVED TO PRODUCE
THIS EXCEEDINGLY COMPLEX
BEHAVIOR.
TO ACCOMPLISH THIS DR. JARVIS'
LAB HAS BEEN AT THE FOREFRONT OF
DEVISING NOVEL TECHNOLOGIES FOR
HIGH QUALITY GENOME SEQUENCING,
ASSEMBLY, EVALUATION AND
ANNOTATION, BEGINNING FIRST WITH
THE HIGHLY CITED AVIAN GENETICS
PROJECT AND THE VERTEBRATE
GENOMES PROJECT, THE EARTH
BIOGENOMES PROJECT AND MOST
RECENTLY, 2 PROJECTS THAT PULLED
ME INTO THE HUMAN P A N-GENOME
CONSORTIUM AND THE TELOMERE TO
TELOMERE CONSORTIUM.
HE WORKS ON GENOMIC AND
MOLECULAR BIOLOGIC TECHNIQUES
TO'D ADVANCE MECH INFORMS OF
VOCAL LEARNING AND MORE BROADLY
GAIN A DEEPER UNDERSTANDING OF
HOW THE BRAIN GENERATES,
PERCEIVES AND LEARNS COMPLEX
BEHAVIORS.
DR. JARVIS RECEIVED HIS DEGREE
FROM HUNTER COLLEGE IN NEW YORK
AND HIS Ph.D. FROM ROCKEFELLER
UNIVERSITY IN MOLECULAR
NEUROBIOLOGY AND ANIMAL
BEHAVIOR.
HE THEN AT AD ON AT ROCKEFELLER
FOR HIS POST DOCTORAL WORK
BEFORE MOVING TO DUKE IN 1998
WHERE HE ROSE TO THE RAIRVEGS OF
PROFESSOR PRIOR TO RETURNING TO
ROCKEFELLER.
DR. JARVIS IS THE RECIPIENT OF
THE PRESTIGIOUS NIH DIRECTOR'S
TRANSFORMATIVE RESEARCH ARK WARD
IN 2019, NIH DIRECTOR'S PIONEER
AWARD, MOST RECENTLY THE EARNEST
EVERETT WORK FROM AMERICAN FOR
CELL BIOLOGY AND THIS IS JUST A
SMALL SMATTERING OF THE LONG
NITTANY OF AWARDS, SPECIAL
LECTURES, AND ACCOLADES THAT
HE'S AMASSED OVER HIS CAREER.
IN 2020 HE WAS 1 OF THE NEW CELL
MENTORS HUNDRED INSPIRING
SCIENTISTS IN AMERICA AND THIS
IS ON TOP OF HIS 250
PUBLICATIONS.
THE TIELTS OF DR. JARVIS' TALK
TODAY IS NEUROBIOLOGY AND
EVOLUTION OF VOCAL LEARNING AND
SPOKEN LANGUAGE.
PLEASE HELP ME TO WELCOME
DR. JARVIS TO THE PODIUM.
>> CAN YOU HEAR ME?
ALL RIGHT.
THANK YOU FOR THAT INTRODUCTION
AND IT'S A PLEASURE TO BE BACK
HERE VISITING COLLEAGUES, HERE
IN THE AUDIENCE AND ELSEWHERE,
AND ALSO UNDER THESE
CIRCUMSTANCES, BE RECOGNIZING A
FORMER PIONEER IN MOLECULAR
BIOLOGY.
SO, THANK YOU SO I WILL BRING MY
SCREEN UP HERE.
OKAY, GREAT, SOMETHING LOOKS
DIFFERENT ABOUT IT.
OKAY, YES THIS WORKS.
SO I WASN'T QUITE SURE HOW MUCH
I'VE BEEN ASKING AROUND TO TALK
ABOUT MY NEUROSCIENCE WORK
VERSUS IME NATIONAL LIBRARY OF
MEDICINICS WORK VERSUS THE
INTERSECTION AND REALLY IT
ACTUALLY ALL THE WORK I DO HAS
AN INTERSECTION BETWEEN GENOMICS
AND NEUROBIOLOGY.
THE GREEN BUTTON?
I KNEW THERE WAS SOMETHING OFF.
THERE WE GO.
OKAY.
GREAT.
THANK YOU.
AND IESM GOING TO REALLY KIND OF
TELL YOU AATORY ABOUT THE TOP
INCREASE IN BODY OF NEUROBIOLOGY
AND SPOKEN LANGUAGE AND HOW
HAVING HIGH QUALITY GENOMES HAS
HELPED US MOVE THIS AREA OF
RESEARCH FORWARD.
SO FOR THE BIOLOGY OF THIS
TOPIC, I WON'T HAVE TIME TO LIKE
COVER EVERYTHING, AND I WROTE A
REVIEW ARTICLE IN 2019, I
ENCOURAGE FOLKS TO READ AND A
SPECIAL ISSUE IN SCIENCE,
THERE'S A LET THAT'S BEEN
PROGRESS SINCE THEN BUT A LOT IS
SIMILAR.
SOME OF THE BASIC PRINCIPLES AND
SO, I'M GOING TO TALK ABOUT THIS
SUBJECT FROM DIFFERENT
BIOLOGICAL LEVELS, BEHAVIORIAL
ANATOMIC AND GENETIC.
STARTING WITH BEHAVIORIAL, WHAT
DO WE MEAN BY VOCAL LEARNING AND
SPOKEN LANGUAGE.
IN OUR EVERYDAY EXPERIENCE, WHEN
WE SAY LANGUAGE AND WHAT DO WE
MEAN BY THAT, WE HUMANS TEND TO
TREAT IT AS A MONETARY TRAIT
EMPLOY BUT WHEN YOU ACTUALLY
LOOK DEEP INTO THE BRAIN
CIRCUITS AND MECHANISMS AND
COMPARATIVE ANALYSIS AND
SPECIES, A LANGUAGE AND SPOKEN
LANGUAGE IN PARTICULAR, CONSISTS
OF MULTIPLE COMPONENTS, AND SOME
OF THOSE COMPONENTS SHOWN IN
BLUE HERE, LIKE VOCAL USAGE
LEARNING, AUDITORY LEARNING ARE
KIND OF MORE UBIQUITOUS AMONGST
THE ANIMAL KINGDOM.
CAN YOU FIND THEM IN MANY
SPECIES, WHERE THERE ARE SOME
THINGS LIKE VOCAL PRODUCTION
LEARNING THAT ARE RARE AND JUST
FOUND ONLY IN A FEW SPECIES
INCLUDING ONLY US HUMANS AND
WHEN YOU TAKE THIS MORE PIE
CHART VIEW OF IT, 1 WOULD DEFINE
SPOKEN LANGUAGE AS A SPECIALIZED
FORM OF LEARNED VOCAL
COMMUNICATION, WITH SOME
COMPONENTS FOUND IN MOST
VERTEBRATES AND HIGHLY
SPECIALIZED LIMITED
PARTNERSHIPPING COMOPPOSITE
BEHAVIORIAL PHENOTYPE
ELEMENTARYS AND A FEW OTHERS IN
A FEW SPECIES, AND WHAT IS VOCAL
PRODUCTION LEARNING AND WHO HAS
IT.
IT'S BEEN FOUND IN ONLY 5 GROUPS
OF MAMMALS, US HUMANS OF COURSE,
LIKE IN JENNIFER LOPEZ AND IN
DOLPHINS AND WHALES, AND BATS,
ELVANTS AND SEALS AND IT'S BEEN
FOUND IN 3 GROUPS OF BIRDS, SONG
BIRDS, PARROTS AND HUMMING
BURREDS.
WHAT ALL THESE SPEC BEYS SHARE
IN COMMON IS THE ABILITY TO HEAR
NOVEL SOUNDS THAT THEY'RE NOT
BORN WITH, INADELY BUT HEAR
NOVEL SOUNDS AND IMITATE THEM
AND PRODUCE THEM AND PASS ON
THOSE VOCAL REPERTOIRES VOCALLY
FROM 1 GENERATION TO THE NEXT.
AND ALSO ALSO DIFFERENT FOR A
COMPONENT USE FEDERAL ARE
LANGUAGE BUT MORE UCIBOLITTOUS,
AUDITORY LEARNING AS I MENTIONED
BEFORE AND EXAMPLE I WILL LIKE
TO GIVE IS YOUR COMMON PET
ANIMALS LIKE DOGS EVEN CHICKENS
AND SO FORTH, CAN LEARN HOW TO
UNDERSTAND HUMAN WORDS LIKE SIT,
[SPEAKING SPANISH ] ]SPEAKING
JAPANESE ], WHOLE SENTENCES LIKE
ROLL OVER, AND GET THE
NEWSPAPER, AND A DOG WILL
UNDERSTAND THOSE THINGS.
SO THE DOG USUALLY WHOOFS INNATE
SOUNDS AND CAN LEARN HOW TO WOOF
IN DIFFERENT CONTEXT FOR FOOD,
ATTENTION ISSUES WHAT WE CALL
VOCAL USAGE LEARNING BUT THAT'S
DIFFERENT THAN VOAK WILL
PRODUCTION LEARNING SO NOW VOCAL
LEARNERS ARE NOT ALL EQUIVALENT
IN THAT REGARD, WITH HUMANS
BEING THE MOST ADVANCED, THE
NEXT MOST ADVANCED ARE PARROTS
AMONGST THE BIRDS AND EVEN
MAMMALS.
AND HERE'S AN EXAMPLE.
>> NEVER SHAKE A BABY BIRD, THAT
WILL BE ABSURD.
>> [IMITATING ]
I WAS A PARAKEET, I'M A DOCTOR,
NOT A PARAKEET.
>> BE I LIKE TO SHOW THIS WHOLE
CLIP AND IT'S FULL, DISCO WAS
RAISED WITH HUMANS FOR A LONG
TIME AND CAN COMBINE MEMORY
RESPONSE IN NEW SENTENCES THAT
WEREN'T NECESSARILY COPIED SO
THERE'S A LOT GOING ON IN THIS
PARROT BRAIN THE SIZE OF MY
THUMB THAT IS VERY REMARKABLE,
VERY MUCH MORE REMARKABLE THAN
WHAT THE DOG CAN DO.
EVEN THOUGH DISCO SAID MEOW WHEN
IT SAW THE DOG, IT GOT THE
CATEGORY RIGHT, THERE IS A CAT
IN THE HOUSEHOLD AND SOMETIMES
GETS THE DOG AND THE CAT MIXED
UP.
SO THAT'S REMARKABLE BUT OUR
CLOSEST RELATIVES THAT SOME
PEOPLE GET EXCITED ABOUT, THE
CLOSEST THEY GET AT SAYING
SOMETHING THAT IS RESEMBLES
LEARNING OR HUMAN SPEECH AND
THIS IN COCO, A GORILLA RAISED
BY HUMANS FOR 35 YEARS VIA SIGN.
>> HOW ABOUT WHEN YOU'RE YOU'RE
COUGHING.
THAT WAS GOOD YOU DID A SNEEZE
ASK THEN A COUGH.
EXCELLENT.
NTHAT IS GOOD AND WHAT'S GOING
ON HERE IS NOT AS GOOD AS WHAT
DISCO THE PARROT CAN DO, WHAT'S
GOING ON HERE IS THAT COCO HAS
GOOD AUDITORY LEARNING, CAN
UNDERSTAND THE HUMAN SPEECH
SOUNDS THIS PERSON IS ASKING,
AND ACTUALLY UNDERSTANDS ABOUT
7000 WORDS PERCEPTUALLY BUT COCO
AND A COLLEGE STUDENT HAS ABOUT
20,000 WORDS, JUST SO YOU KNOW
FOR COMPARISON, BUT COCO CAN'T
EACH GET OUT 1 WORD.
SO WHAT COCO CAN DO THOUGH IS
VOLUNTARILY CONTROL AIR
PULSELESS THROUGH THE VOCAL
TRACK BUT NOT MODULATE THE TRACK
TO MODULATE THE SOUND, IN THIS
CASE IN COUGHING.
SO THAT HAS POSED A QUESTION OF
SCIENTISTS LIKE MYSELF AND
OTHERS ASKING THE QUESTION, WHY
CAN'T WE GET OUR CLOSEST
RELATIVES TO SAY SOMETHING AS
SIMPLE AS THE WORD APPLE WHEN
THESE PARROTS CAN GO FURGT XER
TELL YOU ALL DIFFERENT KINDS OF
VARYS, GOLDEN DELICIOUS,
MACINTOSH AND SO FORTH.
WHAT'S GOING ON HERE WITH
6 MILLION YEARS OF EVOLUTION AND
OTHER PRIMATINGS VERSUS
300 MILLION YEARS WITH THESE
BIRDS.
SO THE NEXT PART OF MY TALK, I
WILL TELL YOU WHAT I THINK IS
GOING ON, CALLED THE MOTOR
THEORY OF VOCAL LEARNING ORIGIN
THAT MAKES A DIFFERENCE.
WE'RE NOT THE ONLY 1S THAT POSE
DIFFERENCES IN VOCAL LEARNING.
THERE ARE 6 HYPOTHESIS I PUT UP
HERE THAT ARE COMMON OUT THERE,
AND IN ALL THESE HYPOTHESIS, THE
GREEN IS THE 4 BRAIN CIRCUITS IN
THE CORTICALE REGIONS FOR
EXAMPLE, RED ARE THE BRAIN STEM
NEURONS THAT CONTROL INNATE
BEHAVIORS OR THE MUSCLES, AND IN
PLURIBU ARE THE VOCAL ORGANS
THEMSELVES LIKE THE LARYNX, AND
[INDISCERNIBLE] IN BIRDS.
BECAUSE OF THAT WE HAVE MORE
NEURAL SPACE TO ACQUIRE OR HAVE
THESE BRAIN CIRCUITS TO CONTROL
COMPLEX LEARNING BEHAVIORS LIKE
SPEECH.
AND I THINK THERE'S SOME
EVIDENCE FOR THIS, WHEN YOU GO
THROUGH THE LITERATURE AND WORK
WE'VE DONE THAT HUMANS HAVE A
BIGGER FOREBRAIN SIZE, BIGGER
CORTEX RELATIVE TO BODY SIZE
THAN MANY OTHER SPECIES THAT MAY
BE CAN ACCOMMODATE EXTRA BRAIN
CIRCUITS AND SONG LEARNING
BIRDS, CERTAINLY--CERTAINLY
SPECIALLY PARROTS AND SONG BIRD
VS A HIGHER DENSITY OF NEURONS
PER CENTIMETER SQUARED RELATIVE
TO OTHER PIRD SPECIES, ACTUALLY
TWICE THE DENSITY, THAT CAN
ACCOMMODATE EXTRA CIRCUITS SO
THERE'S KIND OF SUPPORT FOR
THAT.
WHAT ABOUT DIFFERENCE IN THE
VOCAL ORGAN, I THINK THERE ISN'T
EMPLOY 1 ARGUMENT HAS BEEN IS
THAT IN HUMANS, THE LARYNX IS
MORE DESCENDED IN THE VOCAL
TRACK COMPARED TO OTHER SPECIES
ALLOWING US TO HAVE VARIOUS AND
GREATER SOUNDS.
IT TURNS OUT THAT LIONS CAN
THROW THEIR HEADS UP AND
LENGTHEN THEIR LARYNX AND
INTERPRET MORE SPEECH AND IT
TURNS OUT THAT SONG BIRDS DON'T
HAVE THE EQUIVALENT FOR OTHER
SPECIES AND IF YOU BLOW AIR
THROUGH THE LARYNX OF A MA
CABBING YOU GET ALL THE
DIFFERENT SOUNDS FROM THE HUMAN
LARYNX, THE THIRD HYPOTHESIS IS
THAT IF THE HAVES AND THE HAVE
NOTS IN THE FOREBRAIN.
THAT IS THE VOCAL LEARNING
SPECIES HAVE BEEN ARGUED TO HAVE
THE LANGUAGE MOTOR CORTEX REGION
OR CONTROLS SPEECH THAT YOU
DON'T FIND IN THE NONVOCAL
LEARNING SPECIES AND FURTHER
THAT THIS MAKES A DIRECT
PROJECTION TOET MOTOR NEURONS
THAT CONTROL THE VOCAL ORGANS
AND I THINK THERE IS SOME
EVIDENCE OF THIS, I WILL SHOW
YOU A LITTLE BIT LATER AND
FURTHER, IN VEIN OF THAT SIMILAR
HYPOTHESIS, SOME HAVE ARGUED
THAT NONLEARNING VOCAL SPECIES
ALSO HAD THIS FOREBRAIN CIRCUIT
THAT CONTROL SPEECH BUT THERE'S
A DIFFERENCE THAT IT MAKES AN
INDIRECT PROJECTION TO THE VOCAL
MOTOR NEURONS THAT CONTROL
VOABLGIZATION OR MORE ROBUST
DIRECT PROJECTION THAN THE
NONLEARNERS AND WE WILL COVER
THAT A LITTLE BIT.
ANOTHER HYPOTHESIS IS THAT, THE
AUDITORY CIRCUITS, SECONDARY
AUDITOR AREAS HERE, MAKE A
DIRECT PROJECTION TO BROKERS
AREA HERE, IN THE VOCAL LEARNING
SPECIES OR ENHANCE 1 IN THE
VOCAL LEARNING SPECIES THAT YOU
DON'T FIND IN THE NONVOCAL
LEARNING SPECIES, FOR THOSE THAT
STUDY NEUROBIOLOGY OF LANGUAGE,
THAT WOULD BE THE VESESSICULOUS,
TO THE BR-AREA IN THE REGIONS
AND WE FOUND IT IN MICE FROM
AUDITOR TOW PUTATIVE CIRCUITS, I
DON'T THINK THERE'S A STRONG
EVIDENCE THAT THIS REALLY
DISTINGUISHES VOCAL LEARNS FROM
NONVOCAL LEARNERS, AND FINALLY
COMES FROM THE LINGUISTIC
COMMUNITY, THERE'S AN ARGUMENT
THAT THERE'S A SEPARATE LANGUAGE
MODULE SOMEWHERE IN OUR BRAIN
THAT TELLS THE AUDITORY CIRCUITS
AND THE SPEED CIRCUITS WHAT TO
DO.
HOW TO SYNTAX THINGS TOGETHER,
HOW TO CREATE GRAMMAR AND SO
FORTH WITH THOSE RULES AND I
HAVE NOT FOUND ANY EVIDENCE IN
THE HUMAN LITERATURE BASED UPON
WORK OTHER PEOPLE HAVE DONE AND
WE HAVE DONE IT IN POSTMORTEM
BRAINS FOR A SEPARATE LANGUAGE
MODULE AND INSTEAD I THINK ALL
THE ACTION IS GOING ON IN THE
AUDITORY AND SPEECH PRODUCTION
CIRCUITS PROPER AND WE DON'T
NEED A SEPARATE MASS REGION OF
BRAIN TO TELL THE SPEECH
CIRCUITS WHAT TO DO.
SO HOW DO WE GET HERE AND WHAT'S
GOING ON AT THE MOLECULAR LEVEL,
MY FIRST FORAY INTO THIS AREA
CAME FROM SETTING SONG BIRDS
WHERE WE FOUND THAT WHEN CANARYS
HERE PRODUCE LEARNED SONG LIKE
THIS: [SONG BIRD SINGING ] THIS
IS GENES THAT ARE RESPONSIVE TO
MURAL ACTIVITY IN THE BRAIN AND
YOU SEE THE MRNA PROGUCT IN THE
SONG LEARNING BRAIN REGIONSI
THEY TURN UP AFTER THIS BIRD
SINGS FOR A HALF HOUR, COMPARED
TO THE SURROUNDING BRAIN REGION
AND THE MORE A BIRD SINGS IN THE
HALF HOUR, THE HIGHER
UPREGULATION YOU SEE OF THIS
GENE, IT'S A VERY ENERGETIC
RESPONSE WITHIN A HALF OUR
PERIOD, THERE A LOT OF STUDIES
GOING ON ABOUT THE MECHANISMS OF
THIS REGULATION, WE KIND OF ALSO
USE IT AS LIKE AN MRI SIGNAL, TO
IDENTIFY AUDITORY AND VOCAL
MOTOR AREAS OF THE FOREBRAIN,
AND OTHER BRAIN CIRCUITS OR WHEN
BIRDS ARE SINGING, WE FOUND
USING THIS MOLECULAR MAPPING
APPROACH, BY THE WAY, I WANT TO
SAY THIS IS MOTOR DRIVEN, WHAT
WE SEE HERE, THIS WHITE SIGNAL
FOR THE MRNA FOR THIS GENE.
THAT IS THE BIRD HAS TO SING TO
LEARN VOCALIZATIONS AND IT
DOESN'T LIGHT UP WITH THE
HEARING, IT DOESN'T LIGHT UP
WITH YOU KNOW MOVEMENT OF OTHER
BODY PARTS AND SO FORTH, IT'S
PARTICULARLY SINGING REGULATED
GENE EXPRESSIONS IN A MOTOR
DRIVEN WAY, THAT IS YOU DON'T
NEED SOPHISTICATED MAT O SENSORY
FEEDBACK AT ALL, YOU DON'T NEED
THE LIGHTS ON, THE BIRD CAN ALSO
TRY TO SILENTLY SING, THAT IS
TRY TO MAKE SOUND IF YOU CUT THE
NERVE, IT WON'T VIBRATE THE
MUSCLES AND YOU WILL STILL GET
THE ACTIVATION IN THE BRAIN EVEN
FOR SILENT SINGING SO WE APLAY
THIS APPROACH TO OTHER VOCAL
LEARNING BIRDS LIKE SONG BIRDS,
HUMMINGBIRDS AND PARROTS AND
NONVOCAL LEARNING SPECIES LIKE
PIGEONS AND QUAILS AND WE FOUND
THAT ALL OF THESE SPECIES VOAN
IN BLUE HERE, HAD THIS AUDITORY
PATHWAY, WHETHER YOU'RE A VOCAL
LEARNER OR NONLEARNER ARE
CONSISTENT WITH AUDITORY
CIRCUITS PRESENT IN THE
FOREBRAIN FOR AUDITORY LEARNING,
LIKE THE DOG LEARNING HOW TO SIT
AND SO FORTH THAT YOU DON'T HAVE
TO HAVE VOCAL LEARNING TO HAVE
AN AUDITORY FOREBRAIN CIRCUIT.
HOWEVER, ONLY THE VOCAL LEARNERS
HAD BRAIN REGIONS IN THEIR
SERIES POINTS EASTBOUND RUM THAT
BECAME ACTIVE THAT LIT UP WHEN
THEY'RE PRODUCING THEIR LEARNED
SONGS.
YOU DID NOT SEE THIS IN THE
NONLEARNING SPECIES, INSTEAD YOU
SAW MIDBRAIN CIRCUITS IN DARK
GRAY HERE THAT WERE LIGHTING UP
FOR PRODUCING INNATE SOUNDS AND
WHAT HAPPENED IS YOU HAD THIS
FOREBRAIN CIRCUIT IN YELLOW AND
IN RED, THAT HAVE TAKEN OVER THE
MIDBRAIP CIRCUIT THAT'S ATTACHED
TO IT.
SO IN YELLOW, THEY DESCEND OUT
OF THE FOREBRAIN AND CONTROL
THIS FOR VOCALIZEITIONS AND IN
RED WE KNOW IN SONG BIRDS OF THE
BRAIN RIEJIONS INVOLVED IN THE
ACTIVE LEARNING OF NEW SOUNDS
AND WHAT'S REMARKABLE HERE,
LOOKING AT 50 GENETIC TRAINING
IS THAT ALL 3 OF THESE VOCAL
LEARNING BIRD LINEAGES SEEM TO
HAVE INDEPENDENTLY EVOLVED,
THESE RED DOTS HERE, THESE VERY
SIMILAR CIRCUITS CONSISTING OF 7
BRAIN REGIONS WITH THE ACTIVITY.
NOW IN THE IDENTICAL BRAIN
LOCATIONS BUT SIMILAR.
SO 1 HYPOTHESIS IS THAT THEY
EVOLVED INDEPENDENTLY AND
ANOTHER THAT WAS THERE WAS A
COMMON ANCESTOR AND/OR MAYBE
EVERYBODY HAS IT AT VARIOUS
DEGREES AND IT'S BEEN
INDEPENDENTLY AMPLIFY INDEED
THESE MORE ADVANCED VOCAL
LEARNING SPECIES AND SOMETHING I
DID AND APPRECIATED AT THE TIME
IS MAYBE THE FILL LO
GENERATEDETTIST GOT THE TREE
WRONG.
BECAUSE WHEN THEY WERE LOOKINGA
THE THIS, 1 VOICE SAYS IT PROVES
INTELLIGENT DESIGN, BECAUSE HOW
COULD THIS HAPPEN LIKE THIS IN
60 MILLION YEARS.
I DIDN'T THINK THAT BUT IN
PEOPLE THOUGHT THE TREE COULD BE
WRONG AND MAYBE THEY INHERIT
THESE CIRCUITS FROM A COMMON
ANCESTOR SO THIS GOT ME INVOLVED
IN GENOMICS HEAVILY, AND I GOT
INVOFFED WITH THE GROUP WHO WAS
INTERESTED IN SEQUENCING BIRD
GENOMES TO SEE IF THE TREE WAS
RIGHT OR WRONG FOR MY VOCAL
LEARNING QUESTIONS AND OTHERS
AND WE SEQUENCE A BUNCH OF BIRD
DENOAMS, ABOUT 48 SPECIES AT
THAT TIME REPRESENTING ALL BIRD
ORDERS INCLUDING ALL MY FAVORITE
VOCAL LEARNERS AND THE RED ARE
THE 1S IN WHICH MY LAB HELPED
LEAD OR CO-LEAD AND BLUE IS WHEN
WE COLLABORATED ON AND BLACK ARE
THE 1S THAT SPOKES BENEFITED
FROM THESE GENOMES.
AND FROM THOSE DRAFT QUALITY
GENOMES, WE CREATED GENOME SCALE
N TREE OF BIRDS AND THIS WAS THE
TREE WE CAME UP WITH FOR THESE
48 LINEAGES AND FOUND COMPARED
TO THE TREE THAT WE HAD BEEN
USING FOR DECK'SS BEFORE BEFORE
THAT,--DECADES BEFORE THAT WAS
THE TREE WAS WRONG.
THESE ARE ALL THE NEW
RELATIONSHIPS WE CAME UP WITH.
WHAT ABOUT THE VOCAL LEARNERS IN
THE 3 DOTS IN RED HERE IN YOU
CAN SEE THAT SONG BIRRIER
SURFACESES AND PARROTS ARE
CLOSELY RELATED ALTHOUGH STILL
HAVE NONVOCAL INTERSPECIES
BETWEEN THEM, AND THE
HUMMINGBIRD HAD IT PULLED AWAY
FROM THEM.
IF YOU ARGUE THESE, YOU HAVE TO
GO BACK TO THE TIME OF THE MASS
EXTINCTION OF DINOSAURS THAT
THERE WAS A VOCAL LEARNING
SPECIES THAT EVOLVE THIS ABILITY
INCLUDING IMITATING A HUMAN
SPEECH SOUNDS BEFORE HUMANS WERE
HERE FOLLOWED BY 10 INDEPENDENT
LOSSES, AND SO THAT'S
PARSIMONIOUSLY WE THINK IT'S AN
INDEPENDENT GAIN.
SO IF BIRD CANS COME UP WITH A
SIMILAR SOLUTION OVER THE LAST
65 MILLION YEARS, WHAT ABOUT WE
HUMANS?
AND I THINK IT'S INDEPENDENT.
I THINK I CAN CONADVANCE YOU
IT'S INDEPENDENTLY EVOLVED IN
HUMANS COMPARED TO SONG BIRDS
AND PARONS.
AND SO COMPARING BIRDS TO
HUMANS, THE FIRST LESSON WE
LEARNED HERE IS THAT BRAIN SIZE
DOESN'T MATTER, AND HERE'S A
ZEBRA FINCH BRAIN, AND CORTICALE
FOLDING DOESN'T MATTER, THIS IS
THE PRESENCE OR ABSENCE OF A
PARTICULAR TYPE OF NEURAL
CIRCUIT THAT CONTROLS THE VOCAL
ORGAN AND WHAT IS SAN FRANCISCO
CIRCUIT?
DURING A META,AINAL SIS BETWEEN
THE VOCAL LEARNING STUDIES IN
BIRDS AND HUMANS COMPARED TO
OTHER VERTEBRATES AND NONHUMAN
PRIMATES WE CAME UP WITH THE
FOLLOWING MODEL, WE ARGUED THAT
ALL MAMMALS, HAVE A
[INDISCERNIBLE] LIKE YEAR THAT'S
INVOLVED IN PROCESSING COMPLEX
SOUND.
AND THIS IS WHY A DOG CAN
UNDERSTAND SIT, COME HERE, GET
THE PAWRP --PAPER AND SO FORTH.
THIS IS WHY COCO CAN UNDERSTAND
7000.
BUT THESE SPECIES THAT DON'T
IMITATE SOUNDS WE CAN'T FIND NEM
THIS MOTOR CORTEX REGIONS AND OR
AT LEAST IN THEIR ADVANCE FORMS
MAKE THE DIRECT PROJECTIONS FOR
BEHAVIOR LIKE THE MOTOR CORTEX
AND BROKE AS AN AREA OR OTHERS
IN THE SPEECH ACQUISITION, SOME
PROCESSING AS WELL.
AND SO I ARGUED THAT THESE
REGIONS HERE EVOLVE
CONVERGENTLY, WITH THE REGIONS
I'VE COLORED YELLOW AND RED IN
THE VOCAL LEARNING BIRDS AND HOW
BEING THAT HAVE HAPPENED IN WELL
WE DIDN'T REALLY HAVE AN ANSWER
UNTIL WE CAME ACROSS THIS
DISCOVERY, WHERE WE FOUND THAT
NOT ONLY THE SONG LEARNING BRAIN
REGIONS OF THE SONG BIRD LIGHT
UP WITH THESE IMMEDIATE EARLY
JEEP WHEN IS THEY PRODUCE THEIR
LEARNED SONG, ESPECIALLY IN
HERE, BUT WHEN THEY'RE MOVING
THEIR BODIES, LIKE HOPPING IN
ROTATING WHEEL IN A VERY
COORDINATED FASHION, WE SEE THAT
THERE'S MOTOR DRIVEN GENE
EXPRESSION DIRECTLY SURROUNDING
ALL THE VOCAL LEARNING BRAIN
REGIONS, AND SONG BIRDS, PARROTS
AND HUMMINGBIRDS.
AND THE NONVOCAL LEARNING
SPECIES LIKE A PIGEON OR CHICKEN
THEY HAVE THESE MOTOR DRIVEN
ACTIVATION PAT E-PRESCRIBINGS
BUT WITHOUT THE SONG LEARNING
NUCLEI INSIDE OF THEM.
SO IT SEEMS LIKE THE VOCAL
LEARNING CIRCUITS ARE EMBEDDED
WITHIN THIS MOTOR LEARNING
CIRCUIT AND WHEN WE LOOKEDDA THE
NEURAL CONNECTIVITY OF THE VOCAL
LIMITED PARTNERSHIPPING BRAIN
REGIONS COMPARED TO THE
SURROUNDING NEURONS, IT'S VERY
SIMILAR, LIKE A CORTICALE BASAL
GANG LIAISONNAL THALAMIC LOOP WE
CALL HERE OR DECENDING PATHWAYS
TO CONTROL OTHER BODY PARTS LIKE
WINGS OR LEGS OR HANDS IN
HUMANS.
AND SO WHAT ABOUT HUMANS, WHEN
COLLEAGUES OF MINE WERE DOING
SOMETHING SIMILAR WITH HUMANS
AND GETTING PEOPLE TO LEARN
CHORROGRAPHING SEQUENCE OF
DANCING IN A SCANNER AND FOWP
THAT THE HIGH EVALUATION PROCESS
ACTIVATION DOING LEARNED
SEQUENTIAL MOVEMENTS IN HUMANS
IS DIRECTLY ADJACENT TO THE
MOTOR CORTEX IS BROCCA AREA.
AND ANOTHER THING THAT WAS
DORPHED ARK ROUND THIS TIME AS
WELL, NOT ONLY LEARNING HOW TO
MOVE YOUR BODY TO NOVEL THINGS
YOU HAVE TO IMITATE, BUT IT WAS
FOUND THAT ONLY VOCAL LEARNING
SPECIES CAN LEARN HOW TO DANCE,
AND HERE'S AN EXAMPLE OF A
PARROT WHO WAS RAISED WITH
HUMANS AND LEARNED HOW TO DANCE.
>> HI, SNOWBALL.
SO THIS IS SO MUCH BETTER THAN
DANCING WITH THE TARS.
TELL US BRIEFLY WHAT SNOWBALL
CAN DO AND WE WILL WITNESS IT
FOR OURSELVES.
>> WELL, SNOWBALL CAN DANCE TO A
BEAT AND HE ADJUSTS HIS DANCING
TO FIT THE TEMPO OF MUSIC.
>> THAT'S IMPORTANT THING
DANCING TO THE BEAT OF THE
MUSIC.
HE DOES IT VISUALLY AND
AUDITORIALLY.
>> THERE WE GO.
THIS IS WHAT YOUR DOG CAN'T DO,
OR NONHUMAN PRIMATE CAN'T DO.
ALL RIGHT, THIS 1 I THINK IS
GETTING THE BEAT.
SO THAT'S INCREDIBLE.
WE WILL COME BACK TO THAT IN A
MINUTE.
AND THE OTHER THING WE FOUND
THAT'S ASSOCIATED WITH VOCAL
LEARNING MORE RECENTLY IS THAT
FROM WORK FROM A POST DOC IN MY
LAB, THERE ARE QUITE A BUNCH OF
DIFFERENT SONG BIRD SPECIES FROM
THE WILD AND TESTED THEM ON A
DIFFERENT BATTERY OF COGNITIVE
TESTS OF TRYING TO FIND FOOD
UNDER A CUP OR SO FORTH, MOVING
THE STICK AND DOING SOME
OBSTACLE COURSE TO GET FOOD
REWARD, AND THEN WE FIND THAT
THE BETTER VOCAL SKILLS YOU
HAVE, INCLUDING IMITATING HUMAN
SPEECH SOUNDS, THE ABOUT THE BET
ARE YOU ARE ABOUT PROBLEM
SOLVING, AND THIS ASSOCIATION IS
NOT SEEN WITH REVERSAL LEARNING
OR SELF-CONTROL OR SOCIALIVE
LEARNING OR SPECIFICALLY
ASSOCIATE WIDE PROBLEM SOLVING
AND THERE SEEMS TO BE THIS
CORRELATION BETWEEN VOCAL
LEARNING ABILITY AND THIS 1
COGNITIVE TRAIT HERE AND ALSO
THE ABILITY TO LEARN HOW TO
DANCE.
SO PUTTING ALL THIS TOGETHER, BI
THE WAY, I PUT A LITTLE CIRCLE
HERE, THERE ARE 2 NONVOCAL
LIMITED PARTNERSHIPPING SPECIES,
THE SUBSCENE WHICH IS LIKE THE
CHIMPANZEE OF THE SONG BIRDS AND
A PIGEON.
SO THEY CAN PROBLEM SOLVE BUT
THEY'RE JUST NOT AS GOOD AS THE
VOCAL LEARNERS.
SO PUTTING ALL THIS TOGETHER AND
WHAT I CALL THE MOTOR THEORY OF
VOCAL LEARNING ORIGIN, I ARGUE
THAT ALL VERTEBRATE SPECIES HAVE
PRODUCING INNATE VOCALIZATIONS,
THEY ALL HAVE LEARNING PATHWAYS
FOR LEARNING HOW TO MOVE, WALK,
FLY, AND SO FORTH EMPLOY AND I
ARGUED THAT THIS MOTOR LEARNING
CIRCUIT HAS AN ANTERIOR
FOREBRAIN FOR THOSE AREAS AND
FOR PRODUCING THOSE MOVEMENTS
AND THAT THIS CIRCUIT IS
REPLICATED MULTIPLE TIMES LIKE
YEEN DUPLICATIONS TO GET HOOKED
UP TO DIFFERENT MUSCLE GROUPS TO
CONTROL DIFFERENT BODY PARTS AND
I ARGUED THAT IN THE VOCAL
LEARNING SPECIES IT'S REPLICATED
1 MORE TIME, THROUGH SOME KIND
OF GENETIC MUTATION AND THIS NEW
REPLICATED CIRCUIT TAKES OVER
THE INNATE CIRCUIT FOR VOCAL
BEHAVIOR TO GET THIS EMERGENT
VOCAL LEARNING CIRCUIT THAT'S
SIMILAR TO THE ANCIENT MOTOR
LEARNING PATHWAY.
WITH SOME DIFFERENCE IN
CONNECTIVITY, AS OPPOSE TO
INDIRECT FOR NONVOCAL BEHAVIOR.
SO I CALL THIS BRAIN EVOLUTION
BY BRAIN PATHWAY DUPLICATION
EMPLOY AND FOR DANCING WHAT I
THINK IS GOING ON HERE IS THAT
IN ORDER FOR THIS VOCAL LEARNING
SECOND QUARTER UTR TO WORK, YOU
NEED AUDITORY INPUT TO GO INTO
THE VOCAL MOTOR PATHWAY HERE,
AND CONTROL THE MOST RAPIDLY
FIRING MUSCLES IN THE BODY,
WHICH IS THE LARYNX.
RIGHT?
NOW THAT YOU HAD THIS RAPID
AUDITORY MOTOR INTEGRATION
BETWEEN THE LARYNX AND SOUNDS
YOU HEAR, I ARGUE THAT THAT
MECHANISM CONTAMINATED THE
SURROUNDING MOTOR LEARNING
PATHWAYS AND NOW HUMANS AND
PARROTS AND OTHER VOCAL LEARNING
SPECIES HAVE AUDITORY INPUT THAT
CAN NOW RAPID LOAMACYY INTEGRATE
WITH MOTOR CIRCUITS BROADLY SO
THAT WE CAN MOVE OUR BODIES TO
SOUNDS IN WAYS THAT OTHER
SPECIES CAN AS A RESULT OF VOCAL
LEARNING.
AND FOR PROBLEM SOLVING, I DON'T
KNOW WHAT TO SAY BUT I THINK
MAYBE INCREASING BRAIN SIZE OF
MORE NEURONS PER MILLIMETER
SQUARED ALLOWED THESE SPECIES TO
HAVE MORE COMPLEX CIRCUMSTANCE
UTRS FOR PROBLEM SOLVING BUT
IT'S THE 1 COGNITIVE TRAIT THAT
HAS SOMETHING TO DO WITH VOCAL
LEARNING AND I THINK IT'S WORTH
INVESTIGATING FURTHER.
SO THIS LEADS ME BO THE THIRD
PART OF MY PRESENTATION HERE,
GETTING INTO THE GENOMICS AND
GENETICS BEHIND THIS TRAIT AND
HOW WE STARTED THERE IS THE
FIRLT THING WE HAD DONE A LITTLE
WHILE AGO WAS TO DISSECT OUT THE
VOCAL LEARNING BRAIN REGIONS,
LIKE THE SONG BIRDS AND THE
SURROUNDING MOTOR REGIONS, POP
THEM UP TO THE CAPS, ISOLATE THE
RNA, DNA, AND PROTEINS, PROFILE
THEM TO AT THAT TIME, OLIGIO
MICRO,A RAYS, TO LOOK FOR
DIFFERENT YALE GENE EXPRESSION
INSIDE AND OUTSIDE THESE BRAIN
REGIONS, UP OR DOWN REGULATION
OF CERTAIN GENES AND THE ALAN
BRAIN INSTITUTE WAS DOING
SOMETHING SIMILAR WITH HUMAN
BRAINS, AND MONKEY BRAINS AS
WELL, AND WHAT WE DID IN MY LAB
AT THAT TIME, THIS WAS WHEN I
WAS AT DUKE, WE COMPARED THE
EXPRESSION PROFILE PATTERNS IN
HUMANS AND SONG BIRDS, NONHUMAN
PRIMATES AND NONVOCAL LEARNING
SPECIES AND NOW REPEATED THESE
EXPERIMENTS USING SINGLE CELL
TRANSCRIPTOMICS AND MORE
COMPLETE GENOMES AND WHAT WE
FOUND WHEN WE FIRST DID THE
STUDY, WE FOUND 55 GENES THAT
WERE CONVERGENT BETWEEN SONG
BIRDS AND HUMANS, BUT IN SPEECH
CIRCUITS NOW WE FIND 350 WITH
NEW HIGH QUALITY GENOMES WHEN I
WILL GET TO IN A MINUTE.
AND WHAT ARE THOSE CONVERGENCES,
WE FIND THAT THE SONG BIRD HPC
REGION INVOLVED IN SEQUENCING
LEARNED VOCALIZATIONS HAD
CONVERSION EXPRESSION OF SEVERAL
HUNDRED YEENS OF THE HUMAN
LARYNXIAL CORTEX, WITH LAYERS 2
AND 3 AND LAYER 6 OF THE MOTOR
CORTEX, AND THE RA-NUCLEUS HAD
CONVERGENT OF 5 PLAYERS OF THAT
REGION AND LAYER 5 LIKE THE
NUCLEUS ITSELF ARE THE DIRECT
PROJECTION OUT TO THE MOTOR
NEURONS, SO IT'S NOT EVEN BRAIN
REGION SPECIALIZATION THAT'S
CONVERGENT.
SPECIFIC CELL TYPES HAD
CONVERGENT REGULATION OF THESE
YEENS, SAME WITH THE BASAL
GANGLIA IN PURPLE, THESE ARE
INVOLVED IN SONG LEARNING AND
THIS HELPED IDENTIFY WHICH PART
OF THE HUMAN BRAIN IS THE BRAIN
REGION RESPONSIBLE FOR LEARNING
HOW TO IMITATE SPEECH THROUGH
THIS MOLECULAR CONVERGENCE.
SO WE DID NOT SEE THESE PAT
E-PRESCRIBINGS IN NONVOCAL BIRDS
AND NONHUMAN PRIMATES AND HERE
IS A HEAT MAP OF SOME OF THOSE
JEEPS.
DOWN REGULATION IS RED, AND THE
PATTERN 3 IN THE LEARNING GROUPS
MATCHES THE PATTERN FOR THESE
GENES IN THE PEACH MOTOR CORTEX
OF MUSEUM MANS, MANY DOWN
REGULATE THE YEENS AND A FEW
UPREGULATED 1S.
WE TESTED 1 OF THESE DOWN
REGULATED YEENS AND AXONS
GUIDANCE MOLECULE AND DEMON
TRAITED BY INSITU ORGANIZATION
THAT IS IT IS IN THE RNA NUCLEUS
OF ALL VOCAL LEARNING BIRD
GROUPS, COMPARED TO THE NONVOCAL
DOG REGIONS.
HERE WHERE THE YEEN IS TURNED
DOWN, WE WILL GOET TO IN A
MINUTE WHY I THINK SOME OF THESE
GUIDANCE MOLECULES ARE TURNED
DOWN.
AT THIS SAME TIME EDDIE CHAIN
WAS DOING SOME WORK ON HUMANS,
REMOVING TUMORS IN EPILEPTIC
REGIONS AND TRYING TO FIND THE
BRAIN REGION WITH THESE
ELECTRODES AND WITH THESE
CERTAINLY--CERTAINLY LECT RODES
WE FOUND CONVERGING AREAS WITH
THE SONG BIRDS AND HUMMINGBIRD,
THEY ARE SHOWN IN RED, WITH THE
HIGHEST ACTIVATION WITH SPEECH
PRODUCK, PARTICULARLY MODULATING
THE PITCH OF SOUNDS WHICH IS THE
CHARKTISTIC TRAIT OF VOCAL
LEARNERS.
SO BY THE WAY WE HAVE 2 REGIONS
OF PARROT AS WELL I WON'T GET
INTO SO I THINK THERE ARE 2
PARALENS LENS LENS LENS PATHWAYS
THAT MAKE THEM MORE ADVANCE AND
WHAT'S INTERESTING ABOUT THAT IS
THAT A STUDY CAME OUT SHOWING
THAT THE [INDISCERNIBLE]
ORGANIZATIONS NASSATION OF THE
HUMAN MOTOR CORTEX WHERE WE FIND
THE DORSAL AND VENTRAL LARYNGIAL
MOTOR CORTEX, OF THE SONG BIRDS
THAT THE WHOLE REGION HERE,
HAND, FACE, LEG REGION HAD A
DUAL REPRESENTATION IN THE HUMAN
BRAIN THAT WE ONCE THOUGHT WAS
UNIQUE FOR SPEECH, I'M NOT SO
SURE ANYMORE, WE'RE NOW CHECKING
FOR MICE IN THIS REPRESENTATION
AS WELL, AND OHM THE DORSAL AND
VENTRAL MOTOR CORTEX MAY HAVE 2
PARALLEL PATHWAYS AND MAYBE THE
WHOLE THING IS REGION HERE.
SO THAT WAS THE BEGINNING OF
FINDING THE YEEPS RESPONSIBLE
FOR THIS TRAIT, AT LEAST THE
CONVERGENCE OF THE TRAIT AND MY
LAB WE WANTED TO TAKE THESE
YEENS NOW, AND DO GENETIC
MANIPULATION STUDIES ON THEM,
AND WE STARTED TO FIND THERE
WERE BIG LIMITATIONS OF THESE
FIRST AND SECOND GENERATION
SEQUENCE GENOMES, OR LIKE THE
SPLIT 1 YEEN IT HAS 35 AXONS
SPREAD OUT OVER 15 CONTENTS HERE
IN THE BROWN, DARK BROWN, LIGHT
BROWN MEANS DIFFERENT CONTIGs
THESE BLACK TICK MARKS ARE GAPS
IN THEM.
SO THE GENE WAS INCOMPLETE SO
WE'RE MISSING PARTS OF THE
YEENS, MANY OF THEM ARE
INCORRECTLY,A SEMBLES AND HAD IS
CAUSING INTERESTING REPETITIVE
YEENS WHO ARE FINDING SOME OF
THESE VOCAL LEARNING YEENS HAVE
REPETITIVE REGIONS IN THEIR
REGULATORY REGIONS THAT WE FELT
WERE IMPORTANT FOR THIS
SPECIALIZED REGULATION, THEY
WERE MISASSEMBLED OR NOT
ASSEMBLED AT ALL AND CAUSING
STUDENTS AND POST DOCS IN MY
GROUP TAKING MANY MONTHS,
SOMETIMES A YORE TO RECLONE,
CORRECT THE GENE STRUCTURE AND
NOW YOU'RE NOT JUST STUDYING 1
SPECIES LIKE A MOUSE OR HUMAN,
WE HAVE MANY SPECIES WE'RE
TRYING TO STUDY SO WE HAVE TO
RECLONE THESE GENES FOR MANY
SPECIES AND IT BECAME REALLY
ANNOYING AND ANNOYING WORKING
WITH ARTIFICIAL GENE STRUCTURE
AND SEQUENCE IF YOU DID NOT KNOW
THAT ASK UNKNOWINGLY MAKING
FALLINGS CONCLUSIONS SO RIGHT,A
ROUND THIS TIME I WAS ASKED TO
BECOME LEADER OF THE LARGE SCALE
GENOME PROJECT BECAUSE WITH THE
SUCCESS WITH THE BIRD DEGOAMS,
THEY THOUGHT I COULD DO
SOMETHING WITH VERTEBRATE
GENOMES SO I BECAME CHAIR OF THE
VERTEBRATE GENOME PROJECT AND
ASKED BY MANY OF YOU OF A
COLLEAGUE HERE, THEY JOINED THIS
EFFORT OF WHAT WE CALL DIVERTED
GENOMES PROGEC.
WHERE I AGREED TO HELP LEAD THE
EFFORT UNDER 1 CONDITION AND
THAT CONDITION IS WE TRY TO WORK
WITH THE GENOME COMPANIES AND
OTHERS AND EXPERTS IN THE FIELD
TO GENERATE AS HIGH QUALITY AND
NEAR GAPLESS CHROMOSOMAL LEVEL
ASSEM MYELINS AS POSSIBLE.
AND WHY GO FOR 10,000 SPECIES AT
THE TIME WHAT WE USED TO CALL
THE GENOME 10 K CONSORTIUM BUT
GO THRU ALL 70,000 VERTEBRATE
SPECIES.
NOW I DON'T NEED ALL 7000 FOR MY
VOCAL LEARNING STUDIES ABOUT YOU
IF WE WILL SPEND THE TIME TO DO
IT WE MIGHT AS WELL GO FOR
EVERYTHING, AND TAKE ON AN
AMBITIOUS PRO CHAIR EMPLOY SO IN
THE FIRST SET OF STUDIES WE DID,
I MADE SURE WE HAD A VOCAL
LEARNING SPECIES, HUMMINGBIRD
AND THE FLAGSHIP PAPER OF THIS
STUDY WAS LED BY RON HERE
SITTING IN THE AUDIENCE, AND THE
FIRST STUDY WAS ON HUMMINGBIRD
IN 15 OTHER SPECIES WHERE WE
TESTED A LOT OF DIFFERENT
TECHNOLOGIES, TO TRY TO GET THE
BEST ASSEMBLY POSSIBLE AND
AGAIN, THE COLOR COATING HERE IS
WHAT I HAD BEFORE, IN TERMS OF
GETTING--WHAT LABS ARE GETTING
CREDIT FOR THE DIFFERENT
STUDIES.
AND SO, I DON'T REALLY HAVE TIME
IN THIS NEUROSCIENCE FOCUSED
TALK TO GET INTO ALL THE LESSONS
WE'VE LEARNED BUT I WILL GIVE
YOU THE 3 BIGGEST THAT'S TILL
RELEVANT TODAY IS THAT
HAPLOTYPES OF 1 GIANT REPEAT AND
IF YOU DON'T PHASE YOUR
HAPLOTYPES WELL ENOUGH OR
PROPERLY AND HAVE HIGH SEQUENCE
ACCURACY TO PHASE DUPLICATED
SEQUENCES WITHIN HAPLOTYPES YOU
GET A LOT OF ERRORS AND
PARTICULARLY IN ERRORS WE WERE
CALLING FALSE HAPLOTYPE
DUPLICATIONS, ANOTHER 1 IS THAT
READ LENGTHS NEED TO BE LONGER
WITH THE PETES OF WHAT THEY'RE
SEQUENCING, AND A LOT OF THEM,
SPECIALLY IN SENT RIMERES AND
TELOMERES BUT ESPECIALLY OF
YEENS BUT THEN YOU GOET MESSY
ASSEM MYELIN AND FINALLY,
SOMETHING WE DIDN'T APPRECIATE
AT THE TIME BUT LATER IS THAT
YOU NEED TECHNOLOGY SEQUENCE
THROUGH COMPLEX REGIONS AND SOME
OF THESE LAUNDRY TECHNOLOGIES
LIKE THE PACK BIOSEQUENCING AND
NANO FORCE SEQUENCING WERE
GETTING THROUGH GC RICH ROUGH
ATOM MOTOR REGIONS, WE'RE
MISSING HALF THE PROMOTERS IN
THE YEENS OF THESE ARK SEMESTER
BLES.
WHY?
BECAUSE THEY'RE GC RICH AND
THERE ARE GAPS IN THEM.
AND THERE ARE MANY GENES THAT WE
COULDN'T UNDERSTAND THE
REGULATION OF VOAK WILLA
LEARNING SEGMENTS BA UNITED
STATES WE DID NOT HAVE THE
PROMOTERS.
A NEW ERAPPROVAL FROM SBA
INTRODUCED WITH PACK
BIOSEQUENCING, NOW THEY HAVE GC
RICH REGIONS, AND HIGH QUALITY
GERONTOLOGYSTS NEMS AND THIS
KIND OF INITIATIVE HAS BEEN
ADOPTED AND EXPANDED INVOLVING
SOME OF THE SAME PEOPLE NOW WITH
PULT PEL PROJECTS LIKE THE BAT 1
CAVE PROJECT, GIGA PROJECT,
EARTH BOUND GENOME SEQUENCE
PROJECT.
VERY NATURALISTIC PROJECTS THAT
ARE GETTING GOOD ARK MOUNT OF
MONEY LIKE IN THE UK FOR
[INDISCERNIBLE] OF LIFE, ALL OF
SPECIES IN AFRICA AND HUMAN
PAN-GENOME PROJECT BENEFITED
FROM THIS INITIAL EFFORT OF THE
GENOME PROJECT AND THE
TELOMERE-TELOMERE EFFORT AND FOR
THE GENOME AND MOST RECENTLY THE
PARROT GENOME.
NO TIME TO GET INTO ALL OF THESE
BUT JUST TO SAY THAT MY
MOTIVATION TO LED TO HELPING
THESE PROJECTS WAS BECAUSE ABOUT
VOCAL LEARNING QUESTIONS AND NOW
I WILL TELL YOU SOME SOMETHING
THAT BENEFITED FROM THESE HIGHER
QUALITY GENOMES.
ONE WAS FROM ATAC-SEQ PEAK
REGULATORY REGIONS THAT INVOLVED
IN VOCAL LEARNING.
SO 1 GENE I SHOWED YOU
IMMEDIATELY EARLY YEEN ACTIVATED
BY SINGING OR EARLY MOVEMENT ARK
ROUND THEM, HERE WE FIND THE
PROMOTER IN ATAC-PIQUE AND WE
HPC VERSUS OUTSIDE THE NUCLEUS
AND THIS REGION HERE WE HAVE
RECEIVED THIS PEAK WHICH WE
THINK IS THE REGION SENSITIVE TO
NEURAL FIRING IN THE NEURONS,
THIS WAS MISSING FROM EVERY
SINGLE BIRD GENOME PRIOR TO
THESE HIGH QUALITY ASSEMBLIES.
AND NOW IT'S PRESCRIBINGENT IN
EVERY SINGLE GENOME AND IN THE
DIFFERENT REGIONS OF THESE
DIFFERENT CELL TYPES HERE.
AND FROM THE PROMOTER REGION OF
THIS YEEN.
SO THAT'S A GENE THAT'S
REGULATED INSIDE AND OUTSIDE THE
NUCLEI.
WHAT ABOUT A YEEN THAT
SPECIALIZED SONICALLY LIKE THE
ANDROGEN RECEPTOR AND WE FIEBD
THAT THIS GENE HAS ATEXT
AC-PEAKS SPECIFICALLY OPEN
CHROMATIN REGIONS INSIDE THE
NUCLEUS COMPARED TO THE OUTSIDE
THAT COULD EXPLAIN ITS HIGH
UPREGULATION IN THE SONG
LEARNING NUCLEUS, IN FRONT OF
THE ACTUAL CODING SEQUENCE DOWN
HERE, AND SO, THAT'S JUST 2
GENES, RIGHT?
NOW WHEN WE DID THE ATAC-SEQ
GENOME OF THE HIGH QUALITY ARK
SEMESTER BLES, WE FOUND THAT THE
YEEPS THAT HAD SPECIALIZED
REGULATION, IN THE SONG BIRDING
YOU THIS CLEUS THAT WERE
CONVERGENT WITH HUMANS HAD
PREFERENTIAL ATAC-SEQ PEAK THAT
DIFFERED INSIDE THE NUCLEUS
VERSUS OUTSIDE.
THAT IS THE SONG SPECIALIZED
GENES AND THE SPEED SPECIALIZED
GENES HAD OPEN CHROMATIN REGIONS
IN THE SONG CHROMATIN REGIONS OF
THE BRAIN.
THAT'S WHAT THIS GRAPH HERE
MEANS AND WHEN WE ELECTRIC AT
THOSE OPEN CHROMATIN REGIONS OF
THESE YEENS THAT ARE SPECIALIZED
IN THE SONG LEARNING REGIONS AND
WE ASK, DO THEY HAVE BINDING
SITES AND ENRICHMENT OF
TRANSCRIPTIONA FACTOR BINDING
SITES SHOWN IN THESE SEQUENCE
LOGOS, AND THE ANSWER IS FOR
THE--FOR THE ACTIVITY REGULATED
GENES WE'RE SEEING AND HAVING,
WE FIND THAT THEY HAVE THE
TRANSCRIPTION BINDING SITES IN
THOSE ACTIVITY BINDING YEENS
THAT ARE OPEN INSIDE AND OUTSIDE
THE SONG LEARNING NUCLEI.
FOR THE THE GENES THAT WERE
UPREGULATED IN THE SONG AREAS,
THEY HAVE THE ANDROGEN RICH
BINDING SITE.
FOR JUN.S THAT WERE DOWN
REGULATED, THEY HAD ENRICHMENT
FOR THE NEUROD6 TRANSCRIPTION
BINDING SITE INSIDE THE CIRCUIT
IN THE MOTOR AREAS, SO THIS WAS
QUITE REMARKABLE AND THIS COULD
SMAIN HOW YOU CAN GET HUNDREDS
OF GENES TO DIFFER IN THE SPEECH
AREAS, AND YOU JUST NEED THE THC
EXPRESSION OF A FEW
TRANSCRIPTION FACTORS.
AND SO, LOOKING AT FURTHER, AT
THE ACTUAL NUCLEOTIDE SEQUENCE,
OF THESE OPEN CRIMA TIN REGIONS
INSIDE VERSUS OUTSIDE THE
NUCLEI, AND WE FOUND THAT SOME
OF THEM THAT HAD OPEN CHROMATIN
PEAKS SHOWN WITH THIS LITTLE
BLUE DASH MARK HAD ALSO
ACCELERATED EVOLUTION, WHAT DOES
THAT MEAN, THAT MEANS IN THE
VOCAL LEARNING SPECIES IN SONG
BIRDS, IN PARROTS AND IN
HUMMINGBIRDS THESE REGIONS IN
FRONT OF THESE GENES LIKE
NEURODEDICKS TRANSCRIPTION
FACTOR WOULD RAPIDLY EVOLVING
HERE TO SHOW YOU THE ACTUAL
SEQUENCE, HERE WE HAVE IN BLACK
LETTERS THIS CONSERVED SEQUENCE,
THAT EVERY SINGLE BIRD SPECIES
HAS EXCEPT FOR THE VOCAL
LEARNERS, THE VOCAL LEARNERS HAD
THESE NEWLY EVOLVED SEQUENCES
SHOWN IN RED HERE, NOW BETWEEN
ALL THE VOCAL LEARNERS THAT
EVOLVED IN THEM AND CONVERTED
THIS CONSERVED SEQUENCE, WE HAVE
NO IDEA WHAT IT DOES, INTO AN
ANDROGEN RECEPTOR BINDING SITE,
SO FOR THE ANDROGEN RECEPTOR
TRANSCRIPTION FACTOR.
THAT WILL NOW REGULATE THE
NEUROD6 GENE, IN PUTTING IT
TOGETHER, THE HYPOTHESIS WE'RE
WORKING UNDER IS THAT IN CERTAIN
REGULATORY REGIONS OF THESE
TRANSCRIPTION FACTORS THEY
ACQUIRE NEW MUTATIONS, THESE
LITTLE TICK MARKS HERE, THAT
ALLOW OTHER TRANSCRIPTION
FACTORS OR MOLECULES TO BIND TO
THEM, AND EITHER UP OR DOWN
REGULATION DOWN STREAM GENES
LIKE A TRANSJIPGZ FACTOR WITH
THE NEUROD6 AND CAN INFLUENCE
THE MARKERS THAT ARE INVOLVED IN
FORMING NEUROCONNECKS LIKE SLIT
1.
NOW HOW ARE YOU GOING TO CAUSE A
MUTATION TO CAUSE A SPECIALIZED
REGULATION OF A DOWN REGULATION
OF A GENE INSIDE THE SPEECH
AREA, BUT NOT OUTSIDE.
THE WAY WE THINK THAT'S
HAPPENING IS THAT ONCE THIS NEW
MUTATION APPEARS IN IN
REGULATORY REGION LIKE A GC RICH
REGULATORY REGION, THEN, YOU
HISTONE ACETALATE THAT REGION TO
PREVEBT IT FROM AFFECTING THAT
BRAIN REGION AND TURNING THESE
YEENS DOWN OR UP IN THE
SURROUNDING BRAIN REGIONS SO
THAT'S THE HYPOTHESIS WORKING
UNDER, IF YOU WE LOOK AT THE
GENE ONTOLOGY OF THESE GENES AND
ASK THEM DO THEY HAVE ANY
FUNCTION THAT WOULD RESEMBLE
WHAT YOU WOULD SIGH IN HUMAN
SPEECH AND THE ANSWER IS YES, WE
WILL SAVE TIME HERE JUST IT GO
TO THIS POINT HERE, AND WE FIND
A LOT OF THE UPREGULATED GENES
THAT ARE CONVERGENT BETWEEN SONG
BIRDS AND HUMANS IN THE SPEECH
AREA, WHEN MUTATED, CAUSE POOR
SPEECH DEVELOPMENT OR HAVE
LANGUAGE IMPAIRMENT OR AUTISTIC
VERBAL DEFICITS WITH SPEECH.
AND IT'S SO, WE DON'T THINK IT'S
COINCIDENTAL HERE.
AND SO, LOOKING AT THE HPC AND
RA IS THERE'S 26 YEENS THAT HAVE
THESE ATAC PEAKS THAT I TOLL YOU
ABOUT, HAVE ACCELERATED
EVOLUTION INSIDE THE ATISSUING
AC PEAK REGION AND WHEN MUTATED
CAUSES SPEECH MOTOR DEFICITS AND
HERE'S THE LIST AND I'M LISTING
THESE LIKE THE ANDROGEN
RECEPTOR, AND THE TRANSCRIPTION
FACTOR, AND 1 TRANSCRIPTION
FACER, AND AXON GUIDANCE
RECEPTOR, SLIT 1 LIGAND AND
DPLIEWT MATE RECEPTOR OF ALL
THINGS, AND HERE'S AN EXAMPLE OF
WHAT 1 OF THOSE MUTATIONS DID IS
THE TRANSCRIPTION FACTOR LEADING
TO WILSON'S SYNDROME.
LIKE THERE'S--I WILL NOTICE
THERE'S A SPEECH DEFICIT HERE IN
THIS TRIAL THAN AN AUDITORY
DEFICIT.
[SCREAMING ]
>> SHE'S TRYING TO SAY BUBBLE.
SO BELLA IS 11 YEARS OLD AT THIS
TIME, IS DESCENTLY KROORD
PARTICIPATE COORDINATED
CAN BUT THE BUBBLE BLOWER IN THE
BOTTLE HERE, UNDERSTANDS LOTS OF
WORDS IN HUMAN SPEECH BUT BARELY
CAN GET OUT 1 WORD AT A TIME.
AND ZEB 2 IS UPREGULATED OF THE
NEURONS OF THE MOTOR CORTEX AND
SHE HAS A MUTATION IN THIS GENE
AND WE THINK IT'S DEFINITELY
CONTRIBUTING TO HER DEFICIT.
GRAM 2 B, WE NOTICE THESE IN
HUMANS, IT'S HIGH IN THE
CORTICALE REGION AND IT GOES
DOWN DURING DEVELOPMENT IN THE
SONG LEARNING REGION BECAUSE
FURTHER DOWN THAN IT DOES IN THE
SURROUNDING MOTOR AREAS AND WE
OVEREXPRESSED THE HUMAN VERSION
OF [INDISCERNIBLE] IN THE ZEBRA
FINCH NUCLEUS IN SONG LEARNING
HOOKED UP TO A GFP PROTEIN AND
WE FOUND THAT THE HIGHER THE
EXPRESSION WE OVEREXPRESS GRIN 2
B, THE MORE VARIABLE THE BIRD
SONG BECAME AND THE MORE WE SAW
IT REVERT BACK TO THE JUVENILE
STATE.
WE HAD AN UNFORTUNATE SIDE
CENTER FOR EXCELLENCE ON AGING,
THE BIRDS WOULD STUDDER, AND
WHEN THEY WOULD TRY TO SING TO A
FEMALE FOR COURTSHIP, THEY WOULD
STUDDER, WE THINK IT'S SOMETHING
NERVOUS.
SO THAT'S INTERESTING, AND
THERE'S NO EVIDENT THAT GRIN 2 B
IS INVOLVED IN STUDDERRING BUT 1
NEVER KNOWS.
SO 1 WILL LIKE TETO TEST THE
HYPOTHESIS OF THE FUNCTION OF
THESE GENES LIKE UPREGULATING
SLIT 1 AND SEE IF WE CAN BREAK
THE PROJECTION, DOWN REGULATE IN
A NONVOCAL LEARNER AND TAKE OVER
THE MOTOR CIRCUIT AND SEE IF WE
CAN CREATE A CIRCUIT IN A
NONLEARNING SPECIES, HARD TO DO
IN BIRDS AND TECHNOLOGY, COULD
WE DO THIS IN MICE, ALL RIGHT IN
BUT NOBODY REALLY KNEW ABOUT
WHAT CIRCUITS EXIST IN MICE AND
SO I WILL END OFF IN MY LAST FEW
MINUES HERE, ABOUT HYPOTHESIS
SHE HAS BEEN TESTING IN MICE
WITH THESE GENES AND MICE HAVE
THESE ULTRA SONIC SONGS THAT
THIS NOW IS SINGING TO THIS
FEMALE, HERE'S A SON O GRAM, IT
ALMOST SOUNDS LOAMACY BEING A
SONG BIRD SOUND WHEN PITCHED
DOWN TO OUR HEARING, AS CAN YOU
TELL, IT'S NOT BUT MOSTLY
INNATE, BUT WHAT'S INTERESTING
IS WHEN THEY PRODUCE THEIR ULTRA
SONIC VOCALIZATIONS, AND YOU GET
THOSE LIGHTING UP LIKE WE SAW IN
SONG BIRDS THAT WAS QUITE
SURPRISING, WHEN WE USE
TRANSSYNAPTIC TRACES
INRECYCLINGED IN THE MUSCLES
THEY BACK DOWN THE BRAIN AND GO
UP TO THE SAME REGION OF THE
CORTEX HERE, LAYER 5 NEURONS
LABELED TO INJECTION INTO THE
MUSCLES, AND WHEN WE INJECT
TRACERS, HERE SHOWN AT HIGH
POWER, AND WHEN WE INJECT
TRACERS INTO THIS SUPPOSED VOCAL
ACTIVATED BRAIN REGION, AND LOOK
AT THE MOTOR NEURONS THAT
CONTROL THE VOCAL ORGAN HERE, WE
CAN SEE A LITTLE OF THESE LITTLE
BLACK AXONS HERE COMING FROM
THIS BRAIN REGION UP HERE.
THEY ACTUALLY DO HAVE A DIRECT
PROJECTION AS SEEN IN HUMANS BUT
IT'S VERY SPARSE.
IT'S NOT LIKE--SO HERE'S IN
HUMANS, CAN YOU SEE ALL THESE
FROM A POSTMORTEM BRAIN FROM A
LESION IN LORA RODRIGUEZINGIAL
MOTOR CORTEX REGION AND ALL
THESE LINES GENERATING, HUNDREDS
OF THEM.
SAME IN SONG BIRDS, HUNDREDS OF
AXONS COMING TO INNERIVATE THE
VOCAL NEURONS FOR VOCAL
BEHAVIOR, IN MICE JUST 2 OR 3
MOTOR NEURON.
SO WE THINK IT'S A DEGREE THAN
ABSOLUTENESS.
WHAT ABOUT THIS HERE IN SONG
BIRDS WE DON'T SEE THAT IN A
MOUSE SO DIFFERENT THAN IN
HUMAN.
SO WHAT ABOUT THE FUNCTIONAL
CONNECTIVITY, STUDENT IN MY LAB
DID STUDIES WHERE WE PUT
ELECTRODES IN THE MOUSE BRAIN
AND STIMULATE ALL OVER THE MOTE
OR CORTEX AND WE FOUND THAT IF
WE STIMULATE THESE BRAIN REGIONS
WE CAN GET LAIR INCHLIAL
CONTRACTIONS, SOME FASTER
INDICATIVE OF DIRECT AND
INDIRECT PROJECTIONS ALTHOUGH WE
DON'T GET FULL BLOWN
VOCALIZATIONS.
SO THIS REGION IS CONNECTED
FUNCTIONALLY TO THE LARYNGIAL
MUSCLES IN THE MOUSE BRAIN, AND
WE SEE THIS MOST POSTERIOR
REGION IS MORE IMPIMPLEMENT UPON
THE MUSCLES AND MORE ANTERIOR
REGION FOR THE JAW MUSCLE.
REMINISCENT OF DORSAL AND
VENTRAL MOTOR CORTEX.
SO, AS A GENE THAT REGULATES THE
SLIT 1 YEEN IT'S CALLED FOX P2,
AND MANY OF YOU HEARD ABOUT.
AND SO THAT WAS INTERESTING, SO
WE LOOKEDDA THE FOX P2, AS WELL,
AND FOR THOSE THAT DON'T KNOW
FOX P2 IS A TRANSCRIPTION
FACTOR, CAUSING SPEECH DEFINITE
IN HUMANS AND HERE'S AN EXAMPLE.
[INDISCERNIBLE].
>> SHE'S TRYING TO SAY LAURA.
>> [INDISCERNIBLE]
>> SHE'S TRYING TO SAY
SHEFFIELD.
>> AND HOW OLD ARE YOU.
>> FOUR.
>> SHE'S TRYING TO SAY 4.
I KNOW MY BATTERY'S RUNNING OUT
WHICH MEANS I HAVE 3 MINUES
LEFT.
YES, SO WHAT'S INTERESTING,
THESE MICE HAVE MORE COMPLEX
SYLLABLES THAT THEY PRODUCE WHEN
THEY COURT A FEMALE AND LESS
COMPLEK 1S IN OTHER CONTEXT, AND
WE FIND THAT THE WILD-TYPE MICE
WHEN YOU PLACE THEM IN FRONT OF
A FEMALE, THE MALES, THEY PLACE
THEM IN FRONT.
THEY HAVE THE EXACT MUTATION
COULD NOT SWEECH THESE MORE
COMPLEX SIGNATURESSABLES SO
LAURA HAVING THE SPEECH
PROJECTION, IT'S AFFECTING THE
ABILITY OF VOCALIZATIONS IN THE
FIRST PLACE EVEN FOR INNATE
SOUNDS WHAT ABOUT THOSE LAYER 5
NEURONS, HERE LABELED WITH GFP
FROM THE LARYNGIAL MUSCLE, THEY
ARE THERE IN THE MICE WITH
LAURA'S MUTATION.
HOWEVER INSTEAD OF BEING
LOCALIZED OVER THE CORTEX, THEY
ARE MORE SPREAD OUT OVER THE
CORTEX SO WE THINK THAT FOX P2
IS THE ASSOCIATED WITH THE MOTOR
NEURONS IN THE CORTEX.
AND THIS DATA SHOWS YOU THAT
FEMALE MICE PREFER THE TO LISTEN
TO THESE MORE COMPLEX SONGS THAN
THESE MORE SIMPLE 1S, OKAY, SO,
IF YOU WANT TO PLUG IT IN, YES.
SO WHAT IF WE CAN NOT ONLY PUT
THESE YEENS THAT CAUSE SPEECH
DEFINITES IN MICE BUT ALSO
ENHANCE THEM, AND SO NOW WITH
THESE MORE COMPLETE ASSEMBLIES,
IT'S SHOWING THE PLUG DOWN HERE
BEFORE I RUN OUT OF BATTERY
POWER.
SO WHAT'S GOING ON HERE?
WE THINK IS WHY ARE SOME OF
THESE GENES DOWN REGULATED.
I THINK WHAT'S HAPPENING HERE IN
A NONVOCAL LEARNING SPECIES, I
THE SLIT AND ITS RECEPTOR ARE
REPULSIVE IN THEIR INTERACTIONS.
SO WHEN THE AXONS COME DOWN FROM
THE CORTEX, DURING DEVELOPMENT,
INSTEAD OF SYNAPSING ON TO THE
NEURONS THAT CONTROL VOCAL
BEHAVIOR, THEY GO TO THE
SURROUNDING VENTRICULAR
FORMATION, HOWEVER IN US HUMAN
ANDS THE SONG BIRDS, SLIT IS
TURNED DOWN SO WHEN IT'S
RELEASED FROM THE AXONS, IT
WON'T REPEL THEM BECAUSE, IT
WON'T BE RELEASED IN THIS CASE
EVEN IF THE RECEPTOR IS THERE,
ALLOWING DIRECT CORTICALE
CONTROL OF THE VOCAL ORGANS, AND
BETTER MODULATION OF PITCH.
AND SO, PLEXIN IS ALSO A GENE
THAT'S DOWN REGULATED IN LAYER 5
OF THE MOTOR CORTEX.
SO WHATY WE DID, A POST DOC IN
MY LAB USING CREE TRANSGENIC
MICE IN LAYER 5, WE'RE ABLE TO
KNOCK DOWN PLEXIN AC1 IN LAYER 5
NEURONS OF THE CORTEX AND WE
FOUND THAT--I WILL SHOW IT AT
HIGHER POWER HERE, HERE ARE THE
MOTOR NEURONS LABELED IN GREEN
AND HERE IN WILD-TYPE ANIMAL
VERY FEWAXONS, COMING FROM THE
CORTEX INNOVATING THE LARYNGIAL
MOTOR NEURONS, WHEREAS IN THIS
PLEXIN AC1 KNOCK DOWN WE HAVE
NOT AS MUCH AS WHAT WE SEE IN
HUMANS BUT MANY MORE AXON
SYNAPSING INTO THE NUCLEUS
AMBIGUOUS, AND WE FOUND YOU GET
AN INCREASE IN INNOVATION,
HOMOZYGOUS KNOCK DOWN SO YOU GET
A DOUBLING OF THAT AS WELL.
AND WHEN YOU LOOK AT THE VOCAL
BEHAVIOR OF THESE MICE, THEY'RE
MATURING THEIR VOCALIZATIONS AT
A MORE RAPID RATE THAN THE
WILD-TYPE, THEY'RE ALSO HAVING A
HIGHER, WHERE'S THIS, THE KNOCK
OUTS HERE, THIS, THEY'RE HAVING
A HIGHER DENSITY OF MORE COMPLEX
SYLLABLES, EARLIER ON THAN THE
WILD-TYPE.
AND SO, WE HAVEN'T YET GONE TO
THE POINT OF LIMITED
PARTNERSHIPPING IN THESE MICE
THAT, IS VOCAL LEARNING BUT
THAT'S OUR NEXT EXPERIMENT.
AND SO, I WILL END OFF WITH A
FEW SUMMARY SLIDES HERE.
WHAT DO I THINK IS GOING ON HERE
IN I THINK VOCAL LEARN SUGGEST
NOT AN ALL OR NONE FUNCTION.
IT'S MORE OF A CONTINUUM.
GOING FROM LIZARDS THAT DON'T
VOCALIZE AT ALL TO MICE AND
CHECKENS THAT DO WITH LIMITED
VOCAL MODIFICATION AIBLGHT TO
BAT ANDS SONG BIRDS AND PARROTS
AND SO FORTH, FOR COMPLEX VOCAL
LEARNERS IN HUMANS BY BEING THE
HIGH VOCAL LEARNERS AND THE MORE
YOU GO UP THE LADDER OF THE
CONTINUING THE FEWER SPECIES YOU
HAVE.
AND JUST DENSITY OF INNERVATION
IS WHAT ROGER LEMON PROPOSED FOR
THE LIMB MOTOR NEURONS THAT THE
GREATER INNOVATION OF THE
CORTICALE SPINAL TRACK, YOU HAVE
ON MOTOR NEURONS THAT CONTROL
THE HANDS, THE GREATER MANUEL
DEXTERITY YOU HAVE, I THINK
SPOKEN LANGUAGE IS FOLLOWING A
SIMILAR PRINCIPLE, GREATER
INNERVATION FROM THE BRAIN STEM
CIRCUITS THAT CONTROLLED VOAK
ALTHOUGH AILS, THE MORE ADVANCE
VOCAL ABILITIES HAVE YOU AND AND
THE WORK WE'RE DOING ON MICE
SEEM TO START SUPPORTING THAT
IDEA AND WHAT'S INTERESTING HERE
AND THAT EVEN THOUGH SONG BIRDS
IN HUMANS CAME UP WITH THESE
INDEPENDENTLY, MAYBE FROM THE
SURROUNDING MOTOR AREA, IT
SUGGESTS THAT THE SPEECH PATHWAY
CAN BE UNDERSTOOD BY STUDYING
THEM, DOWN TO THE LEVEL OF
INDIVIDUAL CELL TYPES LIKE THE
PROJECTION NEURONS HERE FROM 1
BRAIN REGION TO ANOTHER OR THE
CORTICALE BASAL GANGLION
THALAMIC LOOP, AND THEY MAKE
PREDICTIONS FROM THE LEVEL OF
CONNECTIVITY, CHROMATIN PEEKS
AND THE GENOME INSIDE THESE CELL
ANDS THEY MAKE PREDICTIONINGS
WHAT HAVE WE COULD EXPECT IN
HUMANS AND SOME OF THOSE ARE
TURNING OUT TO BE TRUE EMPLOY
FROM AN EVOLUTIONARY PERSPECTIVE
WHAT THIS MEANS TO ME IS THAT IN
THIS VERTEBRATE FAMILY TREE
HERE, HERE ARE THESE CORTICALE
REGIONS OF DIFFERENT TYPES IN
GREEN, IT MEANS IF 2 OF THESE
LINEAGES INVOLVE LEARNING AT
INDEPENDENT TIMES WITH CERTAIN
CELL TYPES AND MOLECULAR CHANGES
IN THE LAST 300 MILLION YEARS, I
CAN TELL YOU IF ANOTHER SPECIES
LIKE A CROCODILE OR TURTLE OR
SOME SORT, I CAN PREDICT WHAT
JEERNS WILL BE IPT GREATER
VOLVED, WHERE THOSE WILL BE AT
AND THE LEVELS INCREASE LIEWGZ
OF WINGS, THERE SEEMS TO BE A
LIMITED WAY IN WHICH IT CAN
EVOLVE SUCH A CIRCUIT THAT EVEN
ARK LOWS A PARROT TO IMITATE
HUMAN SPEECH.
FROM THE MOLECULAR TO THE
ANATOMICAL LEVEL AND MAYBE 1
DAY, WE CAN TRANSGENICLY
MANIPULATE OTHER SPECIES AND GET
THEM TO FIGURE OUT HOW TO SING
OUT LOUD.
SO TAKE HOME MESSAGES THAT
COMPLEX BEHAVIOR CANS EVOLVE
MULTIPLE TIMES FROM DEEPLY
HOMOLOGOUS BUT DIVERSE BRAIN
CIRCUIT CELLS AND THE ACTUAL
GENES WERE NOT DISCOVERING NEW
GENES, SO OLD YEENS BEING USE
INDEED NEW WAYS, TRAIT LIKE
SPOKEN LANGUAGE CAN BE
UNDERSTOOD FROM STUDIES OF THESE
DISTANTLY RELATED ANIMALS, AND
CONVERGENT EVOLUTION OF
MECHANISMS OF A TRAIT SEEMS TO
BE ASSOCIATE WIDE SIMILARITIES
AND DISORDERS OF THAT TRAIT.
SO PARTICULARLY FROM AN NIH
PERSPECTIVE, JUST BECAUSE IT'S
CONVERGENT DOESN'T MEAN IT'S NOT
RELEVANT, IT ACTUALLY MEANS IT
IS.
SO I WANT TO THANK ALL THOSE
THAT FUNDED ME INCLUDING THE
INSTITUTES HERE LIKE NINDS AND
NIMH AND SO FORTH AND MOST
RECENTLY THE DIRECTOR'S RO-1
AWARD THAT NEAL MENTIONED I HAD
AND THE PRIVATE FOUNDATIONS
FUNDING AS WELL.
SO I REALLY THANK YOU FOR YOUR
ATTENTION, I CAN NOW TAKE ANY
QUESTIONS THAT YOU HAVE.
[ APPLAUSE ]
>> YOU ARE OF COURSE FREE TO USE
THE MICsOT STEPS.
I HAVE A COUPLE QUESTIONS FROM
ONLINE IF YOU'RE READY.
IN, YEAH.
NFROM EARLIER IN THE TALK, I
THINK IS THE ENHANCED PROBLEM
SOLVING ABILITIES OF VOCAL
LEARNING SPECIES DESCRIBED BY
AUDET AND COLLEAGUES CORRELATED
WITH WORKING MEMORY?
>> THAT'S A GOOD QUESTION.
WITH WORKING MEMORY.
I DON'T KNOW THE ANSWER TO THAT
BECAUSE WE DID NOT ACTUALLY TEST
WORKING MEMORY IN THESE BIRDS.
WE DID TEST ASSOCIATATIVE
LEARNING BUT WE DEPARTMENT TEST
HOW LONG CAN THEY STORE A MEMORY
CAN THEN REPEAT SOMETHING AGAIN.
SO I'M GLAD YOU ASKED, I WILL GO
TALK TO MY POST DOC >> HOWARD
HAD ABOUT 2 SENTENCES.
MAYBE IT WAS AROUND THAT TIME.
DR. OWENS?
>> GREAT TALK.
HAS ANYBODY LOOKED FOR THESE
TYPES OF CIRCUITS THAT CONNECT
MOVEMENT AND VOCALIZATION IN
STROKE?
>> YES, SO, IT DEPENDS ON WHAT
KIND OF STROKE BECAUSE IF IT'S
MORE ANTERIOR PART OF BRAIN, YOU
EXPECT SPEECH PRODUCTION MORE
THAN PERCEPTION.
SO, YES, IN TERMS OF THE
ANALYSIS, THAT WE'VE DONE IN THE
LITERATURE AND TALKING TO
COLLEAGUES THAT A STROKE THAT
ASHINGS SPEECH PRODUCTION IS
GOING TO AFFECT ALSO MOTOR
PRODUCTION DEHAD A FEWS MORE
THAN IT DOES FOR COGNITIVE
BEHAVIORS, THE BRAIN
ORGANIZATION TENDS TO BE SENSORY
AREAS OF MORE SITUATED TO THE
MORE IS THE BACK OF THE BRAIN
AND MORE MOTOR RELATED
FUNCTIONS, THE MORE FRONT, EACH
THOUGH THERE IS A MIXING OF THE
2 SO THE ANSWER IS YES.
>> THANK YOU.
>> PLEASE, GO AHEAD.
DO THE SONG BIRDS HAVE A SIMILAR
TEMPORAL RELATIONSHIP FOR THE
ACQUISITION OF VOCAL LEARNING
THAT HUMANS HAVE?
AND IF SO, HAVE YOU BEEN ABLE TO
FIGURE OUT WHAT THE LIMITING
FACTOR IS FOR THE TEMPORAL
ACQUISITION OF VOCAL LEARNING IN
ANY SPECIES?
>> YES, SO SONG BIRDS UNDERGO A
SENSITIVE OR CRITICAL PERIOD AS
PEOPLE CALL THEM TODAY, OF WHERE
THEY'RE LIKE HUMANS WE LEARN
BEST EARLIER IN LIFE TO THE
LANGUAGE THAT REGREW UP WITH AND
IF WE LEARN LANGUAGE LATER IN
LIFE, PAST PUBERTY IT'S MUCH
HARDER TO DO, IT'S NOT
IMPOSSIBLE, FOR ZEBRA FINCH IT'S
DIFFICULT TO DO, FOR A CANARY
THEY CAN DO IT, PARROTS ARE
BETTER AT IT, BUT JUST LIKE
PARROTS, IT'S STILL EASIER AT AN
EARLY AGE AND THERE ARE GENES
THAT ARE CHANGING
DEVELOPMENTALLY IN THESE SONG
LEARNS CIRCUITS LIKE THE GRIN 2
B WHICH I SHOWED YOU EARLIER
WHICH GOES DOWN IN ADULT, THERE
ARE GENES THAT ARE CHANGING THAT
CORRELATE WITH THESE CRITICAL
PERIODS AND SOME PEOPLE HAVE
BEEN SUCCESSFULLY MANIPULATING
SOME OF THOSE GENES TO TRY TO
REOPEN THEM UP, THE PROBLEM IS
THE STUDDERRING THAT I SHOWED
YOU EARLIER, YOU WILL HAVE SIDE
CENTER FOR EXCELLENCE ON AGINGS
EMPLOY SO 1 IDEA THAT PEOPLE
MIGHT HAVE IS CAN WE REOPEN THE
CRITICAL PERIOD MANIPULATING
THESE YEENS WITH SOME TYPE OF
DRUGS GET SOMEBODY TO LEARN A
NEW LANGUAGE AS IF THEY WERE A
CHILD AND THEN CLOSE IT OFF SO
THEY DON'T FORGET AND CREW OTHER
THINGS UP.
>> ONE MORE ONLINE IF WE CAN GET
TO IT.
>> YEAH.
>> WHAT MIGHT BE THE REASON FOR
WHY CERTAIN BIRDS EVOLVE TO BE
VOCAL LEARNERS.
MANY MAMMALS CAN SOUND AN ARK
LARM, IF NOT TIED TO MATING OR
SHOUTING ALARMS, WHAT PURPOSE
DID THIS TRAIT SERVE IN WILD
PARROTS IN PARTICULAR?
>> YEAH, SO I THINK VOCAL
LEARNING, I THINK THE PRIMARY
REASON VOCAL LEARNING INCLUDING
IN ANCESTRAL HUMANS WAS FOR MATE
ATTRACTION, RIGHT?
AND THAT'S WHAT MOST OF THE
VOCAL LEARNING SPECIES USE THEIR
LEARNING VOCALIZATIONS FOR.
EVEN WHEN YOU HAVE THEIR INNATE
SOUNDS AND SPECIES THAT DON'T
IMITATE, USE THEIR SOUNDS FOR
SEMANTIC INFORMATION LIKE FOOD
AND TREE OR SOMETHING LIKE THAT,
I THINK IT'S FOR MAIN ATTRACTION
BECAUSE IF YOU MODULATE YOUR
VOICE A LOT, YOU KEEP THE OTHER
INDIVIDUAL LISTENING TO YOU.
YOU'RE PAYING ATTENTION TO MORE,
AND PARROTS IN THE WILD, THEY
STEAL LOTS OF VOCALIZATIONS FROM
OTHER SPECIES, THEY STEAL
VOCALIZATIONS FROM DIFFERENT
SOUNDS IN THE WILD AND THAT
BUILDS UP THEIR REPERTOIRE,
MAKES THEM MORE SEXY, OKAY,.
>> I SEE, SO THAT'S IMPORTANT
AND IT'S AN IMPORTANT SELECTING
FACTOR BUT SELECTING AGAINST IT
ARE PREDATORS, SO, THE MORE
VARIED YOUR SOUNDS ARE, THE MORE
LIKELY YOU'RE NOT SOME AUDITORY
SYSTEM WILL NOT HAPPENITUATE TO
AND I WILL REALIZE THAT WHEN I
WAS READING A PARTNERSHIP IN
DUKE GARDENS AND I WAS HEARING A
SONG BIRD AND IT'S SWITCHING THE
SONG EVERY 10 MINUTES, BUT I
LOOKED UP AND I LOOKED UP, AND
I'M NOT THE BIRDS LOVER OR
PREDATOR BUT STILL, SO EVIDENT
THIS MIGHT BE THE CASE THAT SONG
BIRDS KEPT IN CAPTIVITY FOR MANY
GENERATED --DPEN RAYINGS AND EVN
MICE KEPT IN CAPTIVITY PRODUCE
HORMONE VOCALIZATIONS THAN THEIR
COUNTERPARTS.
>> HI, HERRIC, THANK YOU SO MUCH
FOR THAT FASCINATING TALK, SO
WHILE YOU WERE TALKING I WAS
THINKING ABOUT INDIVIDUALS WITH
AUTISM WHO ARE NONVERBAL AND
THEN YOU TALKED A LITTLE BIT
ABOUT IT BUT I THINK THAT THAT
IS JUST VERY, VERY INTERESTING
AND WHAT IS THE STATUS OF THAT
WORK?
ARE YOU ACTIVELY COLLABORATING
WITH OTHERS?
CAN YOU SAY A LITTLE BIT MORE
ABOUT THE RELEVANCE OF YOUR WORK
TO THAT ISSUE?
>> WE HAVE APPLIED FOR SOME
GRANTS USING SONG BIRDSAs A
MODEL AND SOME OF THE GENOMIC
WORK WE HAVE FOR AUTISM BUT WE
NEVER GOT IT FUNDED BUT WE HAVE
PRELIMINARY RESULTS AS OF YET AT
LEAST, RIGHT?
AND THE PRELIMINARY RESULT IS,
SOME OF THOSE REGIONS THAT I WAS
TELLING YOU THAT HAVE
ACCELERATED EVOLUTION, RIGHT IN
AND KUDOS TO THE HIGH QUALITY
GENOMES FOR BEING ABLE TO FIND
THOSE REGIONS, SOME OF THOSE
REGIONS THAT HAVE ACCELERATED
EVOLUTION ARE IN FRONT OF GENES
THAT OVERLAP, SIGNIFICANTLY WITH
YEENS THAT ARE ASSOCIATED WITH
AUTISM, AND PARTICULARLY VERBAL
DEFICITS IN AUTISM, WE THINK THE
LONG STORY SHORT THAT GENES THAT
HAVE CONVERGENT REGULATION IN
HUMAN SPEECH AREAS ARE MORE
LIKELY YOU HADITATIONS IN -
-MUTATIONS IN THEM TO LEAD TO
VERBAL AUTISTIC DEFINITIONS THAN
1 WIEL TRY TO GET FUNDING TO
PROVE IT.
>> ONE LAST QUESTION BEFORE WE
CLOSE DOWN.
>> I'M CURIOUS HOW MUCH YOU
THINK THESE I GUESS ENHANCED
PROBLEM SOLVING ABILITIES AND
SOME OF THE SONG BIRDS COULD BE
DUE TO OR ARE DUE TO A SIMILAR
UNDERLYING MECHANISM THAT
CREATES THE ENHANCED VOCAL
ABILITIES VERSUS THE ENHANCED
VOCAL ABILITIES SORT OF LEADING
TO CERTAIN SOCIAL SELECTIVE
PRESSURES THAT COULD ACTUALLY BE
A CAUSE OF SORT OF ENHANCED
COGNITION AND NEED TO INTERPRET
MEAN XG THINGS LICK THAT.
>> SO YOU'RE WONDERING HOW I
WOULD MAKE THAT CONNECTION
BETWEEN THE 2?
THE ENHANCED VOCAL LEARN XG
COGNITION?
>> YEAH, DO YOU THINK THE
ENHANCED VOCAL LEARNING COULD
PRECEDE THE ENHANCED COGNITION?
>> YEAH, SO I WAS JUST TELLING
THE FOLKS I WAS TALKING TODAY AT
LUNCH, THE POST DOCS HERE IS
THAT WHAT IS THIS RELATIONSHIP?
WE OFTEN, I THINK IT'S SOMEWHAT
UNIVERSAL, WE GREW UP IN SOCIETY
LEARNING THAT LANGUAGE, THE
ABILITY OF LANGUAGE IN HUMANS
HAVE BEEN MORE ADDING TO OUR
SPECIES THAN OTHER SPECIES.
NO 1'S REALLY PROVEN IN THAT
RESULT THAT WE TOLD YOU OF, KIND
OF SUPPORTS THAT I DO THINK THAT
VOCAL LEARNING MIGHT EVOLVE
BEFORE THE ENHANCED COGNITIVE
ABILITIES, BECAUSE BECAUSE IT'S
LIKE THE VOCAL NONLEARNING
SPECIES THAT WE LOOK AT HAVE THE
LEAST PROBLEM SOLVING SKILLS
COMPARED TO VOCAL LEARNERS AND
THE VOCAL LEARNERS THAT HAVE THE
SMALL OR WEAKEST PROBLEM SOLVING
SKILLS ARE MORE LIKE THE
NONLEARNERS SO, I MOON YOU CAN'T
USE A CORRELATION GRAPH TO ARGUE
CAUSATION BUT JUST WHO THE HAVES
AND THE HAVE NOTS SUGGEST THAT
THE VOCAL LEARNING CAME FIRST
BEFORE THE PROBLEM SOLVING
SKILLS.
SO MAYBE TEACH--MAYBE YOU CAN
USE THIS AS A MODEL TO SAY TEACH
YOUR CHILDREN LOTS OF DIFFERENT
LANGUAGES IN COOL AND THEY'LL BE
BETTER PROBLEM SOLVERS LATER ON
IN LIFE.
>> MAYBE A PARROT OR EGG
QUESTION.
>> THAT'S IT.
>> OKAY, I THINK IT'S LEFT FOR
ME TO JUST SORT OF SAY THANK YOU
FOR BOTH BEING HERE BUT JUST FOR
A FANTASTIC AND HIGHLY
STIMULATING TALK.
TOUCH OFFICE OF DIVERSITY
EVERYTHING ESSENTIALLY, WE'RE
HIGHLY APPRECIATIVE OF THAT AND
THERE IS A LITTLE BIT OF A
RECEPTION AFTERWARDS OUTSIDE FOR
COP COFFEE AND COOKIES.
OTHERWISE, JUST A GIANT THANK
FROM ALL OF US AND AN
OVERWHELMING AROUND OF APPLAUSE.
THANK YOU VERY MUCH. GREAT QUESTIONS.