Functional Role of Hippocampal Neuronal Representations

Boston University (Charles River Campus), Boston MA

Investigators

Linked publications & trials

Abstract

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