NIH VideoCast - Connectomics

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Connectomics

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Air date:	Wednesday, March 5, 2008, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 240 * This only includes stats from October 2011 and forward.
Category:	WALS - Wednesday Afternoon Lectures
Runtime:	01:04:25
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Most neuroscientists agree that connectional maps of the brain would have enormous value in developing models of how the brain works and how it fails when subsets of neurons or synapses are missing or misconnected. Such maps would also provide the first detailed information about how the brain's circuits develop and how they change with age. I am especially eager to study such maps from the developing nervous system because of a longstanding interest in the circuit changes that occur during mammalian early postnatal life. My colleagues and I have studied the neuromuscular system where a large proportion of the axonal branches that are established in fetal life are pruned away after birth. This loss, which is sometimes termed "synapse elimination," may be one of the principal ways a mammalian nervous system comes to match the specific demands of a particular epigenetic landscape. In order to study this phenomenon we initially focused on the events occurring at individual synaptic sites where multiple axons compete and all but one are eliminated. Our results have suggested that the competitive events are in part based on the resources available to each axon at a particular synapse. Because each axon has many branches all competing roughly at the same time, the resources available at one site are probably affected by the outcome of synaptic competitions at other neuromuscular junctions that are innervated by the same axons. Hence we have begun to develop techniques to observe all these synaptic interactions at different sites simultaneously. This effort has required computer-assisted axonal tracing and the development of transgenic mice in which different axons are labeled different colors. These Brainbow mice (Livet et al., 2007) give us an opportunity to see the entire connectional maps (or 'connectomes') for muscles and other neuronal circuits. However, at least for the time being, seeking the details of circuits at the finest level of resolution requires electron microscopy. But getting electron microscopic images of large three dimensional circuits is cumbersome. My colleagues Ken Hayworth and N. Bobby Kasthuri have been developing a new kind of microtome and imaging strategy that allows high resolution electron microscopy of hundreds or even thousands of ultra thin (<40 nm) sections that are very large (each section ~4 mm^2 or larger). This automatic tape-collecting lathe ultra microtome (ATLUM) promises to make large scale electron microscopic analysis of volumes routine. It is our hope that connectomic approaches to studying the nervous system will also have utility in answering fundamental questions about disorders in which there is mis-wiring of the brain's circuits. Jeff Lichtman has an AB from Bowdoin (1973), and an M.D. and Ph.D. from Washington University (1980) where he worked for 30 years and was most recently a Professor of Neurobiology. In 2004 he moved to Harvard where he is a Professor in the Department of Molecular and Cellular Biology. He is a member of the newly established Center for Brain Science. Lichtman’s research interests revolve around the question of how mammalian brains accommodate information based on their early experiences. He has focused on the dramatic rewiring of neural connections that takes place in early postnatal development. This work has required development of techniques to visualize the patterns of connections in the nervous system and how they are altered over time. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.

NLM Title:	Connectomics / Jeff W. Lichtman.
Author:	Lichtman, Jeff W. National Institutes of Health (U.S.)
Publisher:
Abstract:	(CIT): Most neuroscientists agree that connectional maps of the brain would have enormous value in developing models of how the brain works and how it fails when subsets of neurons or synapses are missing or misconnected. Such maps would also provide the first detailed information about how the brain's circuits develop and how they change with age. I am especially eager to study such maps from the developing nervous system because of a longstanding interest in the circuit changes that occur during mammalian early postnatal life. My colleagues and I have studied the neuromuscular system where a large proportion of the axonal branches that are established in fetal life are pruned away after birth. This loss, which is sometimes termed "synapse elimination," may be one of the principal ways a mammalian nervous system comes to match the specific demands of a particular epigenetic landscape. In order to study this phenomenon we initially focused on the events occurring at individual synaptic sites where multiple axons compete and all but one are eliminated. Our results have suggested that the competitive events are in part based on the resources available to each axon at a particular synapse. Because each axon has many branches all competing roughly at the same time, the resources available at one site are probably affected by the outcome of synaptic competitions at other neuromuscular junctions that are innervated by the same axons. Hence we have begun to develop techniques to observe all these synaptic interactions at different sites simultaneously. This effort has required computer-assisted axonal tracing and the development of transgenic mice in which different axons are labeled different colors. These Brainbow mice (Livet et al., 2007) give us an opportunity to see the entire connectional maps (or 'connectomes') for muscles and other neuronal circuits. However, at least for the time being, seeking the details of circuits at the finest level of resolution requires electron microscopy. But getting electron microscopic images of large three dimensional circuits is cumbersome. My colleagues Ken Hayworth and N. Bobby Kasthuri have been developing a new kind of microtome and imaging strategy that allows high resolution electron microscopy of hundreds or even thousands of ultra thin (<40 nm) sections that are very large (each section ~4 mm^2 or larger). This automatic tape-collecting lathe ultra microtome (ATLUM) promises to make large scale electron microscopic analysis of volumes routine. It is our hope that connectomic approaches to studying the nervous system will also have utility in answering fundamental questions about disorders in which there is mis-wiring of the brain's circuits.
Subjects:	Axons--physiology Luminescent Proteins Microscopy, Electron Neuromuscular Junction--growth & development Synapses--physiology
Publication Types:	Lecture Webcast
NLM Classification:	WL 102.9
NLM ID:	101470347
CIT Live ID:	6213
Permanent link:	https://videocast.nih.gov/watch=6213

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