Metabotropic Glutamate Receptor Dependent Plasticity: Mechanisms and Mental Retardation

 


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Air date: Monday, November 24, 2008, 12:00:00 PM
Category: Neuroscience
Description: Altered synapse structure and dysfunction is thought to be the origin of many neurological diseases. Motivated by their basic research findings, they discovered altered synaptic plasticity and function in the mouse model of mental retardation and autism, Fragile X Syndrome. Therefore, another aim of the lab is to identify and understand how alterations in synaptic function and connectivity lead to mental retardation and autism. Specifically, they find that LTD is enhanced and abnormally regulated in a mouse model of human mental retardation, Fragile X Syndrome. Fragile X Syndrome is caused by loss of function mutations in an RNA binding protein called Fragile X Mental Retardation Protein (FMRP) which is an RNA binding protein and regulates protein synthesis at synapses. To address these research questions they use a multi-disciplinary approach including electrophysiology, imaging, and biochemical methods in the hippocampus and neocortex, major brain structures implicated in human cognition.

Selected Publications:

Gibson, J.R., Bartley, A.F., Hays, S. and Huber, K.M., "An imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of Fragile X Syndrome" Journal of Neurophysiology, 100(5):2615-26, November 2008

Waung, M.W., Pfeiffer, B.E., Nosyreva, E.D., Ronesi, J.A. and Huber, K.M., "Rapid translation of Arc/Arg3.1 selectively mediates mGluR dependent LTD through persistent increases in AMPAR endocytosis rate" Neuron, 59(1):84-97, July 2008

Ronesi, J.A. and Huber, K.M., "Homer interactions are necessary for mGluR-induced long-term depression and translational activation" Journal of Neuroscience, 28(2)::543-7, January 2008

Volk, L. J., Pfeiffer, B.E, Gibson, J.R. and Huber, K.M., "Multiple Gq-coupled receptors converge upon a common protein synthesis- dependent LTD that is affected in Fragile X syndrome mental retardation." Journal of Neuroscience, 27(43)::11624-34, October 2007

Pfeiffer, B.E. and Huber, K.M., "Fragile X Mental Retardation Protein induces synapse loss through acute postsynaptic translational regulation" Journal of Neuroscience, 27(12):3120-30, March 2007

For more information see our website - NIH Neuroscience Seminar Series
Author: Kimberly Huber, Ph.D., Department of Neuroscience University of Texas Southwestern Medical Center
Runtime: 75 minutes
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CIT File ID: 14794
CIT Live ID: 7128
Permanent link: http://videocast.nih.gov/launch.asp?14794

 

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