Supramolecular Organization of the Postsynaptic Density

描述（由申请人提供）：突触效能的长期改变与学习和记忆有关；这种可塑性的功能障碍与各种神经发育和神经精神疾病有关。该项目的长期目标是阐明突触后密度（PSD）的超分子组织，它在突触信号处理中起着核心作用。这些信息可能最终被证明对设计预防或治疗脑部疾病的新方法非常有用。该资助周期的提案包括三个具体目标：目标1是开发新的电子显微镜工具来研究突触的超微结构，并使用这些工具来研究突触的异常

DESCRIPTION (provided by applicant): 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.