MULTI-SITE ANALYSIS OF HIPPOCAMPAL NEURONAL ENSEMBLES

海马神经元群的多位点分析

• 批准号: 6477154
• 负责人: JAMES J KNIERIM
• 金额: $ 10.98万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6477154
• 关键词: association learning; behavior test; behavioral /social science research tag; brain mapping; dentate gyrus; electrophysiology; entorhinal cortex; hippocampus; laboratory rat; neural information processing; neural plasticity; single cell analysis; thalamic nuclei

A major goal of cognitive neuroscience is to understand behavior and mental processes in terms of the physiological properties of neural circuits. Spatial learning is a prominent paradigm for studying these issues. Mammalian brains encode a cognitive map of the environment, which is used to remember and navigate to important locations. Place cells of the hippocampus, which fire in restricted locations in space, are thought to constitute this cognitive map. The goal of this research program is to understand how place cells and neurons in related areas interact to generate the spatially specific firing of these neurons. The role of hippocampus in learning and memory has been modeled as an associative network with two important properties: pattern completion, the ability to retrieve a stored pattern from degraded input, and pattern separation, the ability to make stored representations of similar inputs more dissimilar. Theoretical and experimental studies hypothesize that (1) the dentate gyrus performs pattern separation; (2) CA3 performs pattern completion; (3) CA1 compares the CA3 output with entorhinal cortex; and (4) the subiculum encodes a universal map for path integration. Powerful, new multi-electrode technology will be used to record dozens of neurons simultaneously for these brain areas to test these hypotheses. These recordings will allow within-animal comparisons of the changes induced in the spatial maps encoded by each area as a result of experimental manipulations. It is hypothesized that (1) dentate gyrus will "remap" an environment in a graded fashion; (2) CA3 will be unaffected by small environmental changes but will form new representations for large changes; (3) CA1 will also be unaffected by small changes, but will tend to remap large changes only partially; and (4) subiculum will be unaffected by these manipulations. The devastating neurological effects of such diseases as Alzheimer's Disease and epilepsy are intimately tied to dysfunctions of the hippocampus and related brain areas. These experiments will generated fundamental insights into the neural interactions between these brain areas that underlie learning and memory, as well as insights into how these mechanisms go awry in these debilitating diseases.

认知神经科学的一个主要目标是根据神经回路的生理特性来理解行为和心理过程。空间学习是研究这些问题的一个突出范例。哺乳动物的大脑编码了一幅环境的认知地图，用来记忆和导航到重要的位置。海马体的位置细胞，在空间中有限的位置活动，被认为构成了认知地图。本研究计划的目标是了解位置细胞和相关区域的神经元如何相互作用以产生这些神经元的空间特异性放电。海马体在学习和记忆中的作用被建模为具有两个重要特性的联想网络：模式完成，从退化的输入中检索存储模式的能力，以及模式分离，使相似输入的存储表征更加不同的能力。理论和实验研究假设：(1)齿状回进行模式分离；(2) CA3完成模式补全；(3) CA1与内嗅皮质CA3输出比较；(4)下托为路径整合编码一个通用地图。强大的新型多电极技术将用于同时记录这些大脑区域的数十个神经元，以验证这些假设。这些记录将允许在动物体内比较由于实验操作导致的每个区域编码的空间地图的变化。假设：(1)齿状回将以分级的方式“重新绘制”环境；(2) CA3不受环境小变化的影响，但在环境大变化时形成新的表征；(3) CA1也不会受到微小变化的影响，但往往只会部分重绘大变化；(4)下骨不会受到这些操作的影响。阿尔茨海默病和癫痫等疾病对神经系统的破坏性影响与海马体和相关大脑区域的功能障碍密切相关。这些实验将对这些大脑区域之间的神经相互作用产生根本性的见解，这些区域是学习和记忆的基础，以及这些机制如何在这些使人衰弱的疾病中出错。