ANATOMY OF ACTIVITY-DEPENDENT SYNAPTIC MODIFICATION

这项拟议研究的长期目标是了解NeuRA是如何 活动改变成人、发育和青少年的突触连通性 E 脑部受损。联合长时程增强/抑制提供了 用于研究活性依赖突触修饰的有用模型 联想活动被认为是突触的正常模式 成人大脑中的修饰。 我之前的研究描述了长期的 内嗅皮层-齿状回系统的增强作用(LTP) 并发现实验中修改的突触就像一个子集 正常存在的Gray-I型突触。建议的研究主题 T 将这一发现概括为生理学的一个解剖学标记 作用于其他脑区，以增强标记物的可信度 D 实用程序。未来的研究可以确定功能修饰与 解剖学方法。 具体地说，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 LTP与远端轴棘EC-CA1突触的相关性。其他研究 将定量地描述正常的形态和组织 EC-CA1突触可加强对任何形态关联的解释 S 已发现的LTP的数量。EC-CA1突触上的LTP不仅 它本身就很有趣，但还有一个额外的重要性。远端 CA1的脊突触在许多方面与EC-DG突触和 关于EC-DG系统和金字塔之间的合理过渡 大脑皮层，实验兴趣的最终焦点。分析了 大脑皮层的突触修饰将从寻求相同的 正常大脑候选区域中Gray-I型突触的亚群 大脑皮层。如果搜索成功，我们就会有提示性的证据 大脑皮层的LTP样突起。 然后，解剖学方法可以用来研究发生在 H 发展，在脑损伤后，在治疗脑损伤后，或 对过度的神经活动(例如， 癫痫)。这一观点的基本原理是相关的活动依赖于 功能和功能障碍的机制及其生化基础 L 突触修饰贯穿有机体的整个生命周期。

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.