Plasticity of Hippocampal Structure and Function

海马结构和功能的可塑性

• 批准号: 6623055
• 负责人: SCOTT M. THOMPSON
• 金额: $ 29.7万
• 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/6623055
• 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）： 突触的结构发生一系列塑性变化。树突棘，在 特别的。显示形状和数量的持续变化 发育，在成熟组织中。并响应他们水平的变化 激活。这些变化的功能后果在很大程度上是未知的。 假设：树突棘结构的差异有重大影响 对突触功效和可塑性的影响。 方法：尽管大量的理论研究提出了具体的方法 脊柱形状变化的功能后果。这些的小尺寸 结构已经排除了对这些假设的任何直接实验检验。我们 将在海马切片培养中创新地使用激光显微光解 在对应于大小的体积内释放笼中的谷氨酸 单树突棘（约1um）。从而将有可能刺激 个体树突丝状伪足或棘，记录它们的电生理学 反应并同时监测其形态。 目标：对假设的关系进行直接测试 几种不同条件下的树突棘结构和功能。 目标 1：确定突触后谷氨酸受体激活在 树突棘的形成。丝状伪足是否有电生理反应或 形态学上谷氨酸的显微光解作用？ 目标 2：确定树突棘形状与突触后的关系 反应能力。树突棘或脊柱的形状如何“变形” 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 释放的谷氨酸或诱导的 LTP 是否受到脊柱形状变化的影响？ 目标 4：确定急性诱发的变化的功能后果 脊柱形状。谷氨酸引起的脊柱形态变化如何影响 谷氨酸微光解作用的电生理反应？ 意义：这些目标的实现将阐明基本原理 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我们的作用提供新的线索。 学习和记忆中的结构突触可塑性以及 具有较高认知功能的神经系统疾病。