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The molecular logic of synapse formation in the brain

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Air date: Wednesday, January 31, 2018, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 633, (343 Live, 290 On-demand)
Category: WALS - Wednesday Afternoon Lectures
Runtime: 01:05:33
Description: NIH Director's Wednesday Afternoon Lecture Series

Dr. Thomas C. Sudhof shared the 2013 Nobel Prize in Physiology or Medicine (with James Rothman and Randy Schekman) for "discoveries of machinery regulating vesicle traffic, a major transport system in our cells."

His current work focuses on the organization of the trans-synaptic signaling machinery that enables synapse formation and specifications as well as synaptic plasticity during development and throughout life. He and his lab members hypothesize that the number, location, and properties of synapses are determined by interactions between presynaptic and postsynaptic cell-surface recognition molecules and/or signaling molecules. They refer to the rules by which these molecules construct circuits as the molecular logic of neural circuits. Several cell-surface and signaling molecules contributing to the molecular logic of neural circuits have been characterized, most prominently presynaptic neurexin cell-adhesion molecules and their various ligands. Although neuropsychiatric disorders such as autism and schizophrenia have high incidence rates, they are poorly understood. Recent advances in sequencing technologies, however, have identified mutations in a large number of genes that predispose to autism and schizophrenia. No common theme unites the affected genes, but a subset of them encodes proteins--including notably the neurexins--that function at the synapse. Dr. Sudhof thus further hypothesizes that at least a subset of autism and schizophrenia syndromes are produced by impairments in the molecular logic of neural circuits: The input/output relations in particular circuits are shifted, but not blocked, and skew the brain's information-processing capacity for a selected set of tasks. In support of this hypothesis, his lab observed that specific autism- and schizophrenia-associated gene mutations in neurexins and their ligands cause selective alterations in a subset of synapses and circuits that induce discrete specific behavioral abnormalities. The lab's analysis of the molecular logic of neural circuits and their impairment in neuropsychiatric disorders has only begun. But the conceptual framework that has been outlined might allow a better understanding of how the brain processes information and of how such information processing becomes altered in autism and schizophrenia.

For his presentation, Dr. Sudhof will describe his lab's work on testing the hypotheses inherent in this conceptual framework, focusing on families of synaptic cell-adhesion molecules such as neurexins and latrophilins. Although incomplete, the studies that he will describe have already led to surprising conclusions about how neural circuits are organized and provide a perspective for future work.

For more information go to https://oir.nih.gov/wals/2017-2018
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NLM Title: The molecular logic of synapse formation in the brain / Thomas C. Südhof.
Author: Südhof, Thomas C.
National Institutes of Health (U.S.),
Publisher:
Abstract: (CIT): NIH Director's Wednesday Afternoon Lecture Series Dr. Thomas C. Sudhof shared the 2013 Nobel Prize in Physiology or Medicine (with James Rothman and Randy Schekman) for "discoveries of machinery regulating vesicle traffic, a major transport system in our cells." His current work focuses on the organization of the trans-synaptic signaling machinery that enables synapse formation and specifications as well as synaptic plasticity during development and throughout life. He and his lab members hypothesize that the number, location, and properties of synapses are determined by interactions between presynaptic and postsynaptic cell-surface recognition molecules and/or signaling molecules. They refer to the rules by which these molecules construct circuits as the molecular logic of neural circuits. Several cell-surface and signaling molecules contributing to the molecular logic of neural circuits have been characterized, most prominently presynaptic neurexin cell-adhesion molecules and their various ligands. Although neuropsychiatric disorders such as autism and schizophrenia have high incidence rates, they are poorly understood. Recent advances in sequencing technologies, however, have identified mutations in a large number of genes that predispose to autism and schizophrenia. No common theme unites the affected genes, but a subset of them encodes proteins--including notably the neurexins--that function at the synapse. Dr. Sudhof thus further hypothesizes that at least a subset of autism and schizophrenia syndromes are produced by impairments in the molecular logic of neural circuits: The input/output relations in particular circuits are shifted, but not blocked, and skew the brain's information-processing capacity for a selected set of tasks. In support of this hypothesis, his lab observed that specific autism- and schizophrenia-associated gene mutations in neurexins and their ligands cause selective alterations in a subset of synapses and circuits that induce discrete specific behavioral abnormalities. The lab's analysis of the molecular logic of neural circuits and their impairment in neuropsychiatric disorders has only begun. But the conceptual framework that has been outlined might allow a better understanding of how the brain processes information and of how such information processing becomes altered in autism and schizophrenia. For his presentation, Dr. Sudhof will describe his lab's work on testing the hypotheses inherent in this conceptual framework, focusing on families of synaptic cell-adhesion molecules such as neurexins and latrophilins. Although incomplete, the studies that he will describe have already led to surprising conclusions about how neural circuits are organized and provide a perspective for future work.
Subjects: Cell Adhesion Molecules, Neuronal--physiology
Nerve Tissue Proteins--physiology
Neural Pathways--physiology
Neurons--physiology
Synapses--physiology
Synaptic Transmission--physiology
Publication Types: Lecture
Webcasts
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NLM Classification: WL 102.8
NLM ID: 101722225
CIT Live ID: 27076
Permanent link: https://videocast.nih.gov/launch.asp?23689