SPINE AND SYNAPTIC PLASTICITY IN MATURE HIPPOCAMPUS

成熟海马的脊柱和突触可塑性

• 批准号: 2904712
• 负责人: KRISTEN M HARRIS
• 金额: $ 32.59万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2904712
• 关键词: afferent nerve; astrocytes; axon; confocal scanning microscopy; dendrites; electron microscopy; hippocampus; laboratory rat; mature animal; neural plasticity; neuroanatomy; structural biology; synapses

DESCRIPTION (Verbatim from the Applicant's Abstract): Dendritic spines are tiny protrusions that stud the surface of principal neurons throughout the brain. They are the primary sites of excitatory synapses, the sites of communication between neurons. The goal of the proposed work is to ascertain the role of synaptic activity in the formation and structure of dendritic spines and their synapses. It had been thought that spines are generated when synaptic activity is enhanced. Our findings show however that spines and synapses are stable during long term enhancement of synaptic activity. Instead we have discovered that dendrites of mature neurons become more spiny within hours after synapses are inactivated. The specific aims of this project are: 1) Establish how soon after inactivation dendrites of mature hippocampal neurons become more spiny. 2) Assess whether dendrites become less spiny after reinstatement of activity. 3) Determine how inactivation and reactivation affect the structure of spines, synapses, and their associated astroglial processes. 4) Determine whether the additional spine synapses are functional. In Aims 1, 2, and 4 quantitative confocal microscopy will be used with field and whole-cell recordings in hippocampal slices from adult rats. In Aim 3 quantitative serial electron microscopy will be used to answer a series of related questions including: i) Do all of the spiny protusions that are detected with confocal microscopy have synapses? ii) Do the additional synapses occur on pre-existing axonal boutons? iii) Is synaptic structure modified during inactivation or reactivation? iv) Are the calcium-regulating organelles in dendritic spines modified by activity? v) Does activity modify the degree of astroglial ensheathment of spine synapses? The reported progress and proposed research present an important new way of thinking about spines and synapses in the mature brain. They suggest that mature neurons maintain an optimal level of activation by regulating spine and synapse number. They could explain why spines are lost after excessive activity, for example, during epileptic seizures. They are also relevant to understanding how spines and synapses might be generated in the mature brain at times when overall brain activity is low. This outstanding renewal application formulates a new and novel view of dendritic spine plasticity that runs counter to established dogma but is consistent with recent findings of other innovative workers in the field, and extends work carried out during the prior application period into significant new areas. Light microscopic and ultrastructural findings as well as neurophysiological data strongly suggest that spine density exhibits multiple states, with certain levels of neuronal activity stabilizing both spine and synaptic number, while increased activity down-regulates both and decreased activity actually up-regulates both, as if neurons strive to maintain stable "activation," irregardless of variations in input activity.

描述(逐字摘自申请者的摘要)：树突很小 覆盖整个大脑的主要神经元表面的突起。 它们是兴奋性突触的主要部位，也是交流的部位 在神经元之间。拟议工作的目标是确定 树突棘形成和结构中的突触活性及其相互作用 突触。人们一直认为，脊椎是在突触活动时产生的 是增强的。然而，我们的发现表明，棘突和突触是稳定的 在突触活动的长期增强过程中。相反，我们发现 成熟神经元的树突在突触后的几个小时内变得更多刺 被灭活了。该项目的具体目标是：1)尽快确定 成熟海马神经元的树突在失活后变得更多刺。 2)评估树突在恢复活动后是否变得不那么刺状。 3)确定失活和重新激活如何影响脊柱结构， 突触及其相关的星形胶质突起。4)确定是否 额外的脊椎突触是有功能的。在目标1、2和4中，量化 共聚焦显微镜将与现场和全细胞记录一起使用 成年大鼠的海马区切片。在AIM中的3个定量系列电子 显微镜将用于回答一系列相关问题，包括：i) 是不是所有用共焦显微镜检测到的刺状突起 突触？Ii)额外的突触是否发生在预先存在的轴突周围？ Iii)突触结构在失活或重新激活过程中是否发生改变？四) 树突棘中的钙调节细胞器被活性改变了吗？ V)活动是否改变了脊椎星形胶质细胞的包膜程度 突触？已报告的进展和拟议的研究提出了一个重要的新 关于成熟大脑中的脊椎和突触的思考方式。他们建议 成熟的神经元通过调节脊椎来维持最佳的激活水平 和突触编号。他们可以解释为什么在过量的情况下脊椎会丢失 活动，例如，在癫痫发作期间。它们还与以下内容相关 了解如何在成熟的大脑中产生脊椎和突触 当整体大脑活动较低的时候。 这份出色的续期申请形成了一个新的、新颖的观点 树突棘的可塑性与既定的教条背道而驰，但 与该领域其他创新工作者的最新发现一致，以及 将前一个申请期内开展的工作扩展到重要的 新领域。光镜和超微结构的发现以及 神经生理学数据有力地表明，脊柱密度表现出 状态，具有一定水平的神经元活动稳定脊椎和 突触数量，而活动增加下调两者并减少 实际上，活动上调了两者，就好像神经元努力保持稳定一样 “激活”，而不考虑输入活动的变化。