Multi-Site Analysis of Hippocampal Neuronal Ensembles

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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.