The proposed study will provide a better understanding of experience- dependent structural plasticity in area CA1 of the hippocampus. The results will provide insights into cellular mechanisms that might contribute to neuropathology such as Alzheirner's Disease as it relates to Long-term potentiation (LTP). LTP is believed to be an important component of some forms of learning and memory. A current focus of neuroscience is to understand the molecular mechanisms of LTP. Recent findings demonstrated an integrin-binding peptide and a heparan sulfate proteoglycan (HSPG)-binding peptide antagonized maintenance of LTP in area CA1 of rat hippocampus. The general goal of the collaborative research proposed is to understand whether integrins and HSPGs play a role in maintenance of LTP and whether they may associate to form adhesive and signaling structures in synapses that are analogous to focal adhesions. Studies are proposed to test the working hypothesis that integrins and HSPGs play a role in LTP and share a signaling pathway that is necessary for maintenance of LTP. Application of peptide on hippocampus slice will reveal whether the effects on LTP are time- dependent. The precise integrins and HSP(3s in area CA1 that affect LTP will be tested for by cross-linking experiments and mass spectrometry mass map analysis of protein cross-linked protein. Immunohistochemistry using antibodies to integrins and HSPGs will verify their expression in area CA1. Patch-clamp introduction of antibody in neurons in area CA1 and whole-cell recording will confirm integrin and HSPG functions in LTP. The expression and co-localization of integrins, HSPGs and components of focal adhesions will be tested for by immunofluorescence and transmission electron microscopy. The proposed project will be conducted as an integrated and coordinated collaboration between Dr. Richard G. LeBaron and Dr. Joe L. Martinez Jr. at The University of Texas at San Antonio (UTSA). Dr. LeBaron will focus on the component of the project that cross-links integrins and HSPGs that may function in synapses and for immunohistochemical analyses. Dr. Martinez will focus on 'the component of the project that tests physiological effects of peptide and antibody on LTP. Dr. LeBaron is an expert in the field of cell adhesion and extracellular matrix interactions and Dr. Martinez is an expert in the field of LTP. Because the proposed research focuses on the functional role of cell-surface adhesion proteins in synapses active in LTP, the experimental design proin6tes a strong and complementary application of the expertise of Drs. LeBaron and Martinez. The proposed collaboration will also provide opportunities for students with diverse backgrounds and fellows at The UTSA to obtain training in the neuroscience techniques that will be implemented to conduct the proposed research.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
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University of Texas Health Science Center San Antonio
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