MULTI-SITE ANALYSIS OF HIPPOCAMPAL NEURONAL ENSEMBLES

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重要范式。哺乳动物的大脑对环境的认知地图进行编码，该地图用于记忆和导航到重要位置。海马体的位置细胞被认为构成了这张认知图，这些细胞在空间中的有限位置上发出信号。这项研究计划的目标是了解相关区域中的细胞和神经元如何相互作用，以产生这些神经元在空间上的特定放电。海马体在学习和记忆中的作用被建模为具有两个重要属性的联想网络：模式完成，从降级输入中检索存储的模式的能力，以及模式分离，使相似输入的存储表征更加不相似的能力。理论和实验研究假设：(1)齿状回执行模式分离；(2)CA3执行模式补全；(3)CA1将CA3的输出与内嗅皮层进行比较；(4)下丘编码用于路径整合的通用地图。强大的新多电极技术将被用来同时记录数十个神经元，供这些大脑区域检验这些假说。这些记录将允许在动物内部比较由于实验操作而导致的每个区域编码的空间地图中的变化。假设(1)齿状回将以分级的方式重新映射环境；(2)CA3将不受小环境变化的影响，但将形成大变化的新表征；(3)CA1也将不受小变化的影响，但倾向于仅部分地重新映射大变化；以及(4)下丘将不受这些操作的影响。阿尔茨海默病和癫痫等疾病的破坏性神经影响与海马体和相关脑区的功能障碍密切相关。这些实验将产生对这些作为学习和记忆基础的大脑区域之间的神经相互作用的基本见解，以及对这些令人衰弱的疾病中这些机制是如何出错的见解。

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.