Spatial Firing Properties of Hippocampal Neurons

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DESCRIPTION (provided by applicant): The neural mechanisms responsible for sophisticated navigational behavior in rats are currently under intense study for at least two key reasons. First, these mechanisms provide an excellent model for the cognitive processes subserved by the human hippocampus. Second, the location-specific discharge of hippocampal "place cells" (pyramidal cells of CA3 and CA1) and of related cell types in nearby brains areas suggests the existence of a map-like representation of the environment whose activity is essential for solving difficult spatial problems. To better understand the relationship between behavior and coordinated neuronal discharge in the hippocampal formation, we will record from single cells as rats perform simple tasks. In one study, we will compare changes of cell activity in different areas after environmental changes too subtle to cause, "remapping" a major change seen when rats are put into a very different, novel environment. As part of the same study, we will investigate a form of pattern completion in CA1 by looking at how discharge in input areas is affected by removing a cue of known salience. We will also ask how accurately changes in goal location choice caused by putting cues into conflict can be predicted from the way the same conflict causes displacements of place cell firing fields. A third experiment arises from an interesting pharmacologic effect that two well-regarded theories make contrary predictions for concerning navigational performance. Thus, dialyzing the GABAA antagonistic picrotoxin into the medial septum increases the precision of place cell firing while greatly reducing the magnitude of hippocampal theta activity. We will therefore ask if precision of goal location choice in a hidden goal task is unchanged or improved, as expected from crisper place cell firing or disrupted as expected from decrements of theta amplitude. Finally, we will continue to record event-specific activity of hippocampal pyramidal cells to test further the idea that these two forms of processing have extremely similar properties despite the strong difference in the kind of information being processed. We hope the proposed work will shed light on the normal operation of a brain structure whose activity is compromised in pathological states including Alzheimer's disease (AD). We also hope that the use of subtle stimulus transformations to cause simpler, more interpretable changes in single cell activity will be a useful new way of analyzing hippocampal function.