Multi-Site Analysis of Hippocampal Neuronal Ensembles

描述（由申请人提供）：海马体形成长期以来一直与学习和记忆过程有关，尽管其处理的确切性质存在争议。直到最近，对该区域的大多数研究都集中在海马体本身的CA1和CA3领域，而对其来自内嗅皮层的皮层输入的关注较少。海马体神经元最显著和最普遍的放电相关是动物的空间定位，尽管这些“位置细胞”的非空间相关性已经被描述过。这一提议将验证通过内嗅皮层进入海马体的两种功能和解剖学上不同的加工流的假设。假设内侧内嗅区将位置信息传递给海马体，海马体构建动物环境的环境和上下文特定的空间表征。侧鼻内区被认为是传递环境中特定物体和物品的信息。海马将外侧内嗅神经元群体活动中编码的经验项目和事件纳入内侧内嗅神经元群体活动中编码的空间表征；这种表征对于灵活的、情境依赖的记忆和潜在的情景记忆是有用的。多电极阵列将用于同时记录CA1和内嗅皮层神经元的集合，以(1)绘制整个内嗅皮层范围内与地点和物体相关的神经活动的分布；(2)测试外侧内嗅神经元是否对物体和气味有反应，而与空间位置无关。(3)测试内侧内嗅神经元是否对空间位置有反应，而与物体存在无关；(4)检验CA1神经元是否对客体-地点关联作出反应。这些实验将提供海马输入的基本特性的关键数据，这是理解海马神经回路进行信息处理和计算的先决条件。由于海马体的损伤与阿尔茨海默病、癫痫、唐氏综合症、自闭症和精神分裂症等多种疾病有关，了解正常动物的神经回路如何运作，将有助于了解这些过程在这些使人衰弱的疾病中是如何出错的。

DESCRIPTION (provided by applicant): The hippocampal formation has long been implicated in learning and memory processes, although the exact nature of its processing is debated. Until recently, most studies of this region have concentrated on the CA1 and CA3 fields of the hippocampus proper, and less attention has been given to its cortical inputs from the entorhinal cortex. The most salient and prevalent firing correlate of hippocampal neurons is the spatial location of the animal, although nonspatial correlates of these "place cells" have been described. This proposal will test the hypothesis that there are two functionally and anatomically distinct processing streams that enter the hippocampus through the entorhinal cortex. The Medial Entorhinal Area is hypothesized to convey place information to the hippocampus, which constructs environment- and context-specific spatial representations of the animal's environments. The Lateral Entorhinal Area is hypothesized to convey information about specific objects and items in the environment. The hippocampus is proposed to incorporate the items and events of experience that are encoded in the population activity of Lateral Entorhinal neurons into the spatial representation that is encoded in the population activity of Medial Entorhinal neurons; such representations are useful for flexible, context-dependent memory and potentially for episodic memories. Multi-electrode arrays will be used to record simultaneously from ensembles of CA1 and entorhinal cortex neurons to (1) map the distribution of place- and object-related neural activity throughout the extent of the entorhinal cortex; (2) test whether Lateral Entorhinal neurons respond to objects and odors regardless of spatial location (3) test whether Medial Entorhinal neurons respond to spatial locations regardless of the presence of objects; and (4) test whether CA1 neurons respond to object-place associations. These experiments will provide critical data on the basic properties of the inputs into the hippocampus, which is a prerequisite for an understanding of the information processing and computations performed by hippocampal neural circuitry. Because damage to the hippocampus has been implicated in such diverse diseases as Alzheimer's disease, epilepsy, Down Syndrome, autism, and schizophrenia, this knowledge of how the circuitry functions in normal animals will provide insight into how these processes go awry in these debilitating disorders.