Plasticity of Hippocampal Structure and Function

海马结构和功能的可塑性

• 批准号: 6460681
• 负责人: SCOTT M. THOMPSON
• 金额: $ 31.76万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6460681
• 关键词: calcium flux; cell cell interaction; cell morphology; cognition; dendrites; electrophysiology; glutamate receptor; hippocampus; lasers; long term potentiation; memory; neural information processing; neural plasticity; neural transmission; neuroimaging; neurons; photolysis; synapses; synaptogenesis; tissue /cell culture

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.

描述（由申请人提供）： 突触会发生一系列塑料结构变化。树突状刺，在 特别的。在形状和数字上显示持续的变化 发育，成熟组织。并回应其水平的变化 激活。这些变化的功能后果在很大程度上未知。 假设：树突状刺结构的差异具有主要 对突触功效和可塑性的影响。 方法：尽管许多理论研究提出了特定的研究 脊柱形状变化的功能后果。这些的小尺寸 结构排除了这些假设的任何直接实验测试。我们 将在海马切片培养物中创新使用激光麦粒溶解 释放与A大小相对应的体积中的笼谷氨酸 单一树突状脊柱（约1UM）。因此，将有可能刺激 单个树突状丝状或刺记记录其电生理学 响应并同时监测其形态。 目的：对假设关系进行直接测试 树突状脊柱结构和功能在几种不同的条件下。 AIM 1：确定突触后谷氨酸受体激活中的作用 树突状脊柱形成。在电生理学或 从形态学到谷氨酸的麦粒液解？ 目标2：确定树突状脊柱形状和突触后的关系 响应能力。树突状脊柱或脊柱的形状如何“变形” 影响对谷氨酸的电生理反应？ 目标3：确定脊柱形状变化对突触的后果 突触可塑性的功效和诱导。是对突触的回应 释放谷氨酸或LTP的诱导，受脊柱形状变化影响？ AIM 4：确定急性诱导变化的功能后果 脊柱形状。谷氨酸诱导的脊柱形态变化如何影响 电生理对谷氨酸​​麦粒液的反应？ 意义：这些目标的成就将阐明基本 突触结构与功能之间关系的原则。 此外，这些实验的结果将为角色带来新的启示 学习和记忆中的结构突触可塑性以及 更高认知功能的神经疾病。