ANATOMY OF ACTIVITY-DEPENDENT SYNAPTIC MODIFICATION

这项研究的长期目标是了解神经元是如何 活动改变了成年人、发育中的人和成年人的突触连接， e 受损的大脑 联合长时程增强/抑制提供了一个 这是一个研究活动依赖性突触修饰的有用模型， 联合活动被认为是突触的正常模式， 成人大脑的变化。 我之前的研究表明， 内嗅皮层-齿状回系统的LTP 发现实验修饰的突触就像是 正常发生的格雷I型突触的一部分 拟议的研究方案 不 为了推广这一发现， 功能到其他大脑区域，以提高标记的可信度， D 效用 未来的研究可以确定功能性修饰， 解剖学方法 具体来说，拟议的研究将使用细胞外生理学和 定量电子显微镜表征超微结构 在远端轴棘EC-CA 1突触LTP的相关性。 其他研究 将定量描述正常形态和组织的 EC-CA 1突触加强对任何形态学特征的解释 S 被发现的LTP EC-CA 1突触的LTP不仅 它本身很有趣，但有额外的重要性。 远侧 CA 1的棘突触在许多方面与EC-DG突触相似， 到EC-DG系统和金字塔之间的合理过渡， 大脑皮层，实验的最终焦点。 分析 大脑皮层中的突触修饰将开始通过寻找相同的 正常脑组织中Gray Ⅰ型突触的研究 皮层 如果搜索成功，我们就能找到 大脑皮层中类似LTP的过程 然后，解剖学方法可以用于研究在心脏病发作时发生的变化。 H 发展，脑损伤后，治疗后治愈脑损伤，或 响应于由过度神经活动（例如， 癫痫）。 这一观点的基本原理是， 机制及其生物化学是功能和功能障碍的基础 L 突触修饰贯穿生物体的整个生命周期。

The long-term objective of the proposed research is to understand how neura activity modifies synaptic connectivity in the adult, the developing, and t e damaged brain. Associative long-term potentiation/depression provides a useful model for studies of activity-dependent synaptic modification becaus associative activity is believed to be the normal mode of synaptic modification in adult brain. My previous research characterized anatomical correlates of long-term potentiation (LTP) in the entorhinal cortex (EC)-dentate gyrus (DG) system and found that the experimentally modified synapses are just like a subset of the normally occurring Gray type-I synapses. The proposed studies attem t to generalize this discovery of an anatomical marker of physiological function to other brain regions so as to enhance the marker's credibility a d utility. Future studies could then identify functional modification with anatomical methods. Specifically, the proposed studies will use extracellular physiology and quantitative electron microscopy to characterize the ultrastructural correlates of LTP at the distal axospinous EC-CA1 synapses. Other studies will quantitatively describe the normal morphology and organization of the EC-CA1 synapses to strengthen interpretations of any morphological correlat s of LTP which are discovered. LTP at the EC-CA1 synapses is not only interesting in its own right but has an additional importance. The distal spine synapses of CA1 are similar in many respects to the EC-DG synapses an to the reasonable transition between the EC-DG system and the pyramids of cerebral cortex, the eventual focus of experimental interest. Analyses of synaptic modification in cerebral cortex will begin by seeking the same subset of Gray type-I synapses in candidate regions of normal cerebral cortex. If the search is successful, then we will have suggestive evidence for an LTP-like process in cerebral cortex. The anatomical method could then be used to study alterations that occur wi h development, after brain injury, after treatments to cure brain injury, or in response to pathologies induced by excessive neural activity (e.g. epilepsy). The rationale for this view is that related activity-dependent mechanisms and the biochemistry thereof underlie functional and dysfunction l synaptic modification throughout the life span of the organism.