Long-term modifications in synaptic efficacy are implicated in learning and memory;dysfunction of this plasticity is implicated in a variety of neurodevelopmental and neuropsychiatric disorders. The long-term goal of this project is to elucidate the supramolecular organization of the postsynaptic density (PSD), which plays a central role in synaptic signal processing. This information may ultimately prove very useful in designing novel approaches to the prevention or treatment of brain disorders. The proposal for this funding cycle includes three specific aims:
Aim 1 is to develop new electron microscopic tools to study the ultrastructure of synapses, and to use these tools to study abnormalities of the PSD in mouse models of autism and schizophrenia.
Aim 2 is to examine how actin filaments attach to the PSD, to study the organization of two isoforms of a protein that links actin to the PSD, and to study two PSD-associated enzymes that control Rho-family proteins (molecular switches that modulate actin remodeling).
Aim 3 is to study the alignment of presynaptic release sites with postsynaptic receptors, and to explore possible disruptions in synaptic structure and receptor expression in mice that have mutations in synaptic adhesion molecules.

Public Health Relevance

Developmental disability, autism, and severe psychiatric disease represent a substantial drain on our country's resources, and a terrible human cost. By examining the structure of synapses in rodent brain, this research may provide a better understanding of the biological basis of these disorders, potentially leading to new approaches to prevention or treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS039444-10A1
Application #
8372575
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Talley, Edmund M
Project Start
1999-10-01
Project End
2017-06-30
Budget Start
2012-09-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2012
Total Cost
$330,895
Indirect Cost
$112,145
Name
University of North Carolina Chapel Hill
Department
Physiology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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