Role of Class I MHC in Synaptic Refinement &Plasticity

Harvard University (Medical School), Boston MA

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Abstract

DESCRIPTION (provided by applicant): These experiments are intended to gain insight into the synaptic mechanisms by which class I MHC affects the refinement and plasticity of hippocampal synapses. Because members of the class I MHC gene family are expressed by neurons in many brain regions, the findings may help determine general principles governing activity-dependent events in other brain regions. The specific aims of the proposal seek to: first, determine the subcellular localization of class I MHC in hippocampal pyramidal cell synapses; second, to determine if class I MHC is necessary for development of hippocampal fine structure; third, determine if class I MHC is necessary for basal synaptic transmission in hippocampal pyramidal cells. Thus, the results from these experiments will directly address the hypothesis that short-term changes in synaptic strength lead to long-term changes in synaptic structure. Further, deducing MHC l's role in synaptic refinement and plasticity could provide crucial insight into a number of debilitating diseases for two reasons: first, neurodevelopmental and neurodegenerative diseases may wreck havoc on the brain via selective targeting of neurons with specific expression patterns of MHC I. Second, a genetic linkage exists between MHC I and a number of diseases with a neurological component, including: multiple sclerosis, ALS, epilepsy, spinocerrebellar ataxia, Huntington's disease, Parkinson's disease, and dyslexia.