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可塑性变化。树突棘，在 很特别。显示期间形状和数量的持续变化 在成熟的组织中发育。并对其水平的变化做出反应 激活。这些变化的功能后果在很大程度上是未知的。 假设：树突棘的结构差异有一个主要的 对突触效能和可塑性的影响。 方法：尽管许多理论研究都提出了具体的 脊柱形状变化的功能后果。这些东西的小尺寸 结构排除了对这些假设的任何直接实验测试。我们 将创新地利用激光显微光解在海马片培养中 释放笼中谷氨酸的体积相当于 单个树突棘(约1微米)。因此，将有可能刺激 单个树突的丝状足或刺，记录它们的电生理 并同时监测它们的形态。 目标：对假设的关系进行直接测试 几种不同条件下树突棘的结构和功能。 目的1：确定突触后谷氨酸受体激活在大鼠脑内的作用。 树突棘的形成。丝状伪足对电生理有反应还是 从形态上对谷氨酸进行微光分解？ 目的2：确定树突棘形状与突触后的关系 响应性。树突或脊椎的形状是如何“变形”的？ 影响谷氨酸的电生理反应？ 目标3：确定脊柱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 脊柱形状变化对释放谷氨酸或诱导LTP有何影响？ 目标4：确定急性诱发的脑血管病变的功能后果 脊椎形状。谷氨酸诱导的脊柱形态改变如何影响 谷氨酸微光分解的电生理反应？ 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理。 此外，这些实验的结果将为研究这一角色提供新的线索。 结构突触可塑性在学习和记忆中的作用 认知功能较高的神经系统疾病。

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.