Multisite analysis of hippocampal neuronal ensembles

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PROJECT SUMMARY The hippocampus is a brain structure that is critical for normal learning and memory functions. One of the first brain regions to deteriorate in Alzheimer's Disease is the entorhinal cortex, the key processing stage between the neocortex and the hippocampus. This degeneration correlates with the memory deficits that are among the first cognitive symptoms of the disease. To understand why hippocampal damage causes such severe memory deficits, it is necessary to understand the basic computational functions of this brain region. The entorhinal cortex is divided into two regions: the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). A long-standing theory hypothesizes that the hippocampus supports the conscious recall of autobiographical events (“episodic memory”) by binding the different aspects of an experience—the sights, sounds, thoughts, emotions, etc., experienced at a moment in one's life—onto a framework that represents the spatial context in which that experienced occurred. The MEC is thought to provide the hippocampus with this spatial framework, whereas the LEC is thought to represent the “item and events” of experience. Much is known about how the MEC represents space, but how the LEC represents experience is much less understood. The specific aims of this project are to test the hypothesis that the LEC encodes the location of attended items in the external world relative to the individual (i.e., an egocentric framework), whereas the MEC encodes both the locations of attended external items and the location of the individual in a world-centered coordinate system (i.e., an allocentric framework). Furthermore, we will test the hypothesis that the hippocampus incorporates new information within the spatial framework by creating new place fields when the rat performs a discrete, attentive behavior known as head scanning, especially when that behavior is accompanied by a reward. Finally, we will test the hypothesis that the hippocampus explicitly encodes the identity of nonspatial, surface texture cues experienced at a given location by modulating the firing rate of the place cell at that location (so-called rate remapping). The results of these experiments will provide crucial knowledge about how the brain encodes and stores representations of events within their spatial contexts, which underlies our abilities to form conscious memories of our life experiences.