SYNAPSES AS INFORMATION PROCESSING-MEMORY ELEMENTS

突触作为信息处理记忆元素

• 批准号: 3396285
• 负责人: WILLIAM B LEVY
• 金额: $ 14.31万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396285
• 关键词: afferent nerve; association learning; autoradiography; cognition; conditioning; dendrites; electron microscopy; electrophysiology; memory; microscopy; neural information processing; neural inhibition; neural initiation; neural transmission; neuroanatomy; silver impregnation; synapses

Brief, high-frequency conditioning stimulation of the entorhinal afferents to the dentate gyrus produces long-term potentiation (LTP) of this monosynaptic response. It is now clear that a diversity of modifications exists, all of which may occur simultaneously, although to varying extents and at different, although adjacent, locations. The four long-term, associative modifications are excitatory synaptic potentiation, excitatory synaptic depression, and potentiation and depression of what may be disynaptically activated, inhibitory synapses mediating feedforward inhibition (or its functional equivalent). Our electrophysiological research seeks to determine the independence of these four phenomena, particularly the temporally associated conditions of pre- and postsynaptic activity/inactivity that lead to each modification. Anatomical studies seek the cellular bases of these diverse modifications. It appears that larger synapses correlate with excitatory synaptic potentiation. Fewer synapses may be associated with excitatory synaptic depression. A primary aim of this project is to dissociate the correlates of excitatory synaptic potentiation from synaptic depression and mere afferent activity during conditioning. The proposed research would characterize further the physiological and anatomical changes. We week: 1) to continue characterization and quantification of the ultrastructural correlates of the LTP-conditioning paradigm; 2) to define and distinguish the variety of modifications accompanying LTP and LTP-like conditioning paradigms; 3) to characterize the modifiability and to determine inferentially the role of granule cell dendritic spines and dendritic branching patterns as determinants of the spatiotemporal summation of inputs upon the granule cell; 4) to determine if the absolute number of synapses is altered with conditioning, and 5) to relate our work on modification as a function of use (associative activity/inactivity) to contemporary trends and problems in neuroscience. The methodologies employed include quantitative light and electron microscopy, stereology, electron microscopic autoradiography, light microscopic-Golgi methods, extracellular neurophysiology, and computer modeling of anatomical data. Understanding how synaptic connectivity can be altered in the adult brain and the cellular bases of these alterations should contribute to the development of rational treatments for brain injury due to disease, trauma, stroke, and aging.

对内嗅传入神经进行短暂的高频调理刺激 齿状回产生长时程增强（LTP） 单突触反应。 现在很明显，多种修改 存在，所有这些都可能同时发生，尽管程度不同 且位于不同但相邻的地点。 四是长期、 联想修饰是兴奋性突触增强、兴奋性 突触抑制，以及可能的增强和抑制 双突触激活的抑制性突触介导前馈 抑制（或其功能等同物）。 我们的电生理学 研究旨在确定这四种现象的独立性， 特别是突触前和突触后的时间相关条件 导致每次修改的活动/不活动。 解剖学研究寻找这些不同修饰的细胞基础。 看来较大的突触与兴奋性突触相关 增强作用。 较少的突触可能与兴奋性突触有关 沮丧。 该项目的主要目的是分离相关因素 突触抑制和单纯突触增强的兴奋性突触增强 调节过程中的传入活动。 拟议的研究将进一步表征生理和 解剖学的变化。 我们本周：1）继续表征和 LTP调节的超微结构相关性的量化 范例; 2）定义和区分各种修改 伴随的 LTP 和类似 LTP 的调节范式； 3）表征 颗粒细胞的可修改性并推断其作用 树突棘和树突分支模式作为决定因素 颗粒细胞输入的时空总和； 4）确定 如果突触的绝对数量通过调节而改变，并且 5) 将我们关于修饰的工作联系起来作为使用的函数（关联 活动/不活动）到神经科学的当代趋势和问题。 采用的方法包括定量光和电子 显微镜、体视学、电子显微镜放射自显影、光 显微高尔基体方法、细胞外神经生理学和计算机 解剖数​​据建模。 了解如何改变成人大脑中的突触连接 这些改变的细胞基础应该有助于 开发针对因疾病、创伤、 中风和衰老。