The hippocampus is believed to be necessary for learning sequences and for disambiguation, andcomputational models predict that different subregions of the hippocampal formation playdistinct roles in memory. However, these predictions have not been tested experimentally, and no one hasdemonstrated a causal relationship between patterns of activity in hippocampus and animal behavior.This project will address both issues in animals performing a delayed non-match to place (DNMP) task in a 'T'maze.
In Aim 1, we will study the emergence of context-sensitive sequences neural activity in region CA1 ofdorsal hippocampus as animals learn the task, and compare activity from the Sample, Delay, and Choicephases of the task in both correct and incorrect trials. Positive results will allow us to develop a stronger tiebetween electrophysiological and behavioral data.
In Aims 2 -3, we will extend this approach to region CASand dorsolateral entorhinal cortex (EC). Computational models predict that CAS neuronsshould generate queued representations of temporal context, and that separate populations in EC shouldcode for temporal context and and sequences of paths from the current location.
In Aim 4, we will test thehypothesis that the period of the theta rhythm can be divided into encoding and retrieval phases.
In Aim 5, we will study spatial trends in receptive fields of context-sensitive neurons.
In Aim 6, we will test thehypothesis that cells encoding a given temporal context (left-turn vs. right-turn trial) are spatially clustered.
In Aim 7, we will stimulate selected hippocampal neurons in an attempt induce 'false memories' in theDNMP task.
Aim 7 is technically challenging, but if successful, provides direct evidence that manipulation ofhippocampal acitivity leads to alterations in episodic-like memory.The long-term goals of the proposed work are to establish a causal relationship between hippocampalactivity and behavioral performance in episodic-like tasks, and to understand more completely howmemories of relevant episodic experiences are encoded in entorhinal cortex and in regions CA1 and CAS ofhippocampus. Such levels of understanding will be of great value in working toward treatments for memorydisorders. The value of the planned experiments is not contingent on positive results from the high-risk Aim7.
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