2011 |
Carr, Margaret F |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Dynamics of Information Flow in the Hippocampal Circuit @ University of California, San Francisco
DESCRIPTION (provided by applicant): The hippocampus and adjacent structures in the medial temporal lobe are essential for the ability to rapidly encode new memories for facts, places and events. When exploring a novel environment, the hippocampus must reconcile incoming sensory experience with stored representations to form a new memory. My long- term research goals are to understand how ongoing behavior shapes circuit function and how this ability may be altered in pathological states. In this research proposal, I focus on how behavioral state and novelty shape circuit function in the hippocampus. Specifically, this proposal focuses on subfield CA1, which serves as the main output of the hippocampus, and its inputs, layer III of the entorhinal cortex (EC) and hippocampal subfield CA3. These inputs are thought to convey information to CA1 about current sensory experience (EC) and internally stored representations (CA3). While these regions have been the subjects of many investigations, almost nothing is known about how CA1 dynamically couples with and integrates input from CA3 and EC during learning. Here, I propose to use multi-electrode implants to record simultaneous neural activity in CA1, CA3, and the EC of rats as animals explore an initially novel environment and learn about an initially novel task. My specific aims are: Specific Aim 1: To test the hypothesis that during learning, behavioral state continuously modulates information flow through the hippocampal circuit. Specific Aim 2: To test the hypothesis that learning enhances the temporal alignment of representations across the hippocampal circuit. Accomplishing these specific aims will reveal how behavior and learning actively shape circuit function in the hippocampal-entorhinal circuit and more broadly, this work will contribute to our understanding of how experience shapes information processing in the brain. This research is a prerequisite to understanding how these dynamics go awry in various neurological disorders that involve the hippocampal formation. PUBLIC HEALTH RELEVANCE: The hippocampus is a part of the brain that is important for our everyday ability to remember new facts, places and events. Dysfunction of the hippocampus is associated with age-related memory loss, autism spectrum disorders, schizophrenia, depression, and addiction, but we do not understand how aberrations in hippocampal function contributes to the complex behavioral changes observed in these diseases. The proposed research will help us better understand the normal functioning of the hippocampal circuit, leading to better understanding of and ultimately treatments for these disorders.
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