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。哺乳动物的大脑编码了一个环境的认知地图，用于记忆和导航到重要的位置。海马体的位置细胞在空间中的有限位置放电，被认为构成了这幅认知地图。这项研究计划的目标是了解相关区域的位置细胞和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属性的关联网络：模式完成，从退化输入中检索存储模式的能力，以及模式分离，使存储的相似输入表示更加不相似的能力。理论和实验研究假设：（1）齿状回执行模式分离;（2）CA 3执行模式完成;（3）CA 1将CA 3输出与内嗅皮层进行比较;（4）下托编码路径整合的通用地图。强大的新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，以测试这些假设。这些记录将允许在动物内比较由每个区域编码的空间图中诱导的变化，作为实验操作的结果。假设：（1）齿状回将以分级的方式“重新映射”环境;（2）CA 3将不受小的环境变化的影响，但将形成对大的变化的新表示;（3）CA 1也将不受小的变化的影响，但将倾向于仅部分地重新映射大的变化;（4）下托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大脑区域之间的神经相互作用的基本见解，这些大脑区域是学习和记忆的基础，以及对这些机制在这些使人衰弱的疾病中如何出错的见解。

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.