Plasticity of Hippocampal Structure and Function

描述（由申请人提供）： 突触在结构上经历了一系列的可塑性变化。树突棘，在 特别的。显示形状和数量的持续变化， 在成熟组织中发育。并根据其水平的变化， activation.这些变化的功能后果在很大程度上是未知的。 假设：树突棘结构的差异是一个主要的 对突触功效和可塑性的影响。 方法：虽然许多理论研究表明， 脊柱形状变化的功能后果。这些小尺寸 结构已经排除了这些假设的任何直接实验测试。我们 将在海马切片培养中创新性地使用激光显微光解 以在对应于细胞大小的体积内释放笼状谷氨酸， 单个树突棘（约1um）。因此，有可能刺激 单个树突丝状伪足或刺，记录它们的电生理 反应并同时监测其形态。 目的：直接检验以下假设关系： 树突棘的结构和功能在几种不同的条件下。 目的1：确定突触后谷氨酸受体激活在脑缺血中的作用。 树突棘形成。丝状伪足是电生理反应还是 谷氨酸的显微光解 目的2：探讨树突棘形态与突触后神经元突触后电位的关系。 响应能力。树突棘或棘的形状如何“变形” 影响对谷氨酸的电生理反应 目的3：确定脊髓形状的整体变化对突触的影响。 突触可塑性的功效和诱导。是对突触的反应 释放谷氨酸或诱导LTP的影响脊柱形状的变化？ 目的4：确定急性诱导的变化的功能后果， 脊柱形状。谷氨酸诱导的脊柱形态学变化如何影响 对谷氨酸的微光解的电生理反应？ 意义：这些目标的实现将阐明 突触结构和功能之间关系的基本原则。 此外，这些实验的结果将使人们对这种作用有新的认识。 学习和记忆中的结构突触可塑性，以及 高级认知功能的神经系统疾病。

DESCRIPTION (provided by applicant): Synapses undergo a range of plastic changes in structure. Dendritic spines, in particular. display ongoing changes in both shape and number during development, in mature tissue. and in response to changes in their level of activation. The functional consequences of these changes are largely unknown. Hypothesis: Differences in the structure of dendritic spines have a major impact on synaptic efficacy and plasticity. Approach: Although numerous theoretical studies have suggested specific functional consequences of changes in spine shape. the small size of these structures has precluded any direct experimental tests of these hypotheses. We will make innovative use of laser microphotolysis in hippocampal slice cultures to release caged glutamate within a volume corresponding to the size of a single dendritic spine (about 1um). It will thus be possible to stimulate individual dendritic filopodia or spines, record their electrophysiological responses and monitor their morphology simultaneously. Objective: Perform direct tests of the hypothesized relationships between dendritic spine structure and function under several different conditions. Aim 1: Determine the role of postsynaptic glutamate receptor activation in dendritic spine formation. Do filopodia respond electrophysiologically or morphologically to microphotolysis of glutamate? Aim 2: Determine the relationship of dendritic spine shape and postsynaptic responsiveness. How does the shape of a dendritic spine or spine 'morphing' affect electrophysiological responses to glutamate? Aim 3: Determine the consequences of global changes in spine shape on synaptic efficacy and induction of synaptic plasticity. Are responses to synaptically released glutamate or induction of LTP affected by changes in spine shape? Aim 4: Determine the functional consequences of acutely induced changes in spine shape. How do glutamate-induced changes in spine morphology affect electrophysiological responses to microphotolysis of glutamate? Significance: The achievement of these aims will elucidate the fundamental principles underlying the relationship between synaptic structure and function. Furthermore, the results of these experiments will cast new light on the role of structural synaptic plasticity in learning and memory, as well as in neurological diseases of higher cognitive function.