Connectomics |
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Air date: | Wednesday, March 05, 2008, 3:00:00 PM |
Category: | Wednesday Afternoon Lectures |
Runtime: | 75 minutes |
NLM Title: | Connectomics [electronic resource] / Jeff W. Lichtman. |
Series: | NIH director's Wednesday afternoon lecture series |
Author: | Lichtman, Jeff W. National Institutes of Health (U.S.) |
Publisher: | [Bethesda, Md. : National Institutes of Health, 2008] |
Other Title(s): | NIH director's Wednesday afternoon lecture series |
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: | Government Publications Lectures |
Download: | Download
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NLM Classification: | WL 102.9 |
NLM ID: | 101470347 |
CIT File ID: | 14343 |
CIT Live ID: | 6213 |
Permanent link: | http://videocast.nih.gov/launch.asp?14343 |
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Enhanced Audio Podcast | 1:04:25 | Enhanced Video Podcast | 1:04:25 |