A hippocampal mechanism for considering possibilities

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DESCRIPTION (provided by applicant): The hippocampus is critically involved in flexible learning tasks, particularly in spatial navigation, reversal, and episodic-memory tasks and tasks that require planning and decision-making. In tasks with a spatial component, hippocampal cells show a strong spatial firing correlate (termed "place fields"). Because it is possible to record large neural ensembles from hippocampus, and because the set of place fields generally cover the entire environment, it is possible to reconstruct location from hippocampal neural ensembles. In spatial decision tasks, non-spatial information (episodic memory, decisions to be made, etc.) is projected onto the spatial domain. This means that the spatial tuning of place cells provides leverage with which to examine the dynamics of hippocampal representations on decision tasks. Using new reconstruction methods that enable the interpretation of representation of spatial location from neural ensembles at very fast (e.g. tens of ms) timescales, we have recently observed a reliable, repeatable phenomenon whenever rats paused at a decision point on a maze: During most behaviors, location reconstructed from the ensemble was an accurate representation of the rat's location within the maze. However, at decision points, the reconstructed location swept ahead of the rat, first down one potential path, and then down the other. After alternating back and forth for 500- 1000 ms, the representation returned to the location of the animal and the rat began running again. These non-local reconstructions reliably stretched forward of the animal rather than behind the animal. Our working hypothesis is that this phenomenon reflects a choice-consideration, path-, or goal-planning process. The objective of this proposal is to test this hypothesis and further our understanding of the mechanisms underlying these observations. Our plan of attack is to record neural ensembles in a cued-choice task and to determine the behavioral situations in which these phenomena occur. We will identify the location of the rat when these phenomena occur (e.g. does this only occur at choices?) and the locations which get reconstructed to (e.g. does it sweep all the way to the goal?). We will then characterize the hippocampal contribution to the phenomena through detailed comparison with afferent structures and a detailed analysis of hippocampal local field potentials, interneuron and pyramidal cell firing patterns, and the interaction between them. The work proposed here will increase our understanding of the role of the hippocampus in spatial navigation, episodic memory, and decision-making. Using novel analysis techniques applied to neural ensemble recordings, we have recently observed that hippocampal ensembles transiently encode the available choices when rats pause at decision-points. This objective of this proposal is to understand the mechanisms underlying this novel phenomenon, which may reflect a choice- consideration process. Understanding the mechanisms of the normal decision-making process will have implications for patients in which that process has broken down such as in anxiety disorders or other cognitive disorders such as Alzheimer's disease and Schizophrenia.