BEHAVIORAL AND PLACE CORRELATES OF HIPPOCAMPAL NEURONS

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The broad, long-term objective of this project is to describe the nature of hippocampal neural activity in cognitive functions subserving learning and memory. This knowledge will contribute to our understanding of the neurological basis of memory disorders consequent to hippocampal-system dysfunction in aging and disease. There are two specific aims of the project: 1) to clarify the basic functional correlates of firing in hippocampal principal neurons in rats performing memory tasks, and 2) to describe the topographical organization of those correlates in the hippocampal cortex. The proposed experimental design exploits new methods in chronic unit recording to correlate spike activity with sensory and behavioral events in discrimination learning and spatial navigation tasks for which performance is dependent on hippocampal pathways. Computerized analyses involving physiological and behavioral measures will be used to uncover the optimal correlate of spike activity to key task events. Particular attention will be paid to the degree to which unit activity can be explained by two parameters prominent in previous descriptions of hippocampal units, "behavioral" parameters, including stimuli and responses of learned significance, versus "place" or allocentric spatial position of the animal. Comparison of the firing correlates for the same cell both across parameters within each task, and across separate tasks will be used to infer the higher-order functional attributes common across task variations. Based on neuropsychological data, our working hypothesis is that these higher order attributes will reflect encoding of stimulus configurations by hippocampal neurons. Specific experiments will focus 1) on the identification of functional correlates reflecting configurations of task events, 2) on the development of these correlates during the course of learning, and 3) on their disappearance after disconnection of hippocampal pathways. The proposed experiments involve recording from several single- units simultaneously using two different kinds of multichannel microelectrode. These methods will not only increase the efficiency of data collection, but will also permit an exploration of the anatomical organization of functional correlates within the hippocampus. Analyses will focus on comparisons of the functional correlates among the major hippocampal regions and on comparisons among near and distant neighboring cells recorded simultaneously. These analyses will be used both to generate and to confirm hypotheses about the processing mechanisms reflected in the functional correlates of individual neurons.