The maturation of learning and memory abilities during childhood is critical for the development of the individual. Before trying to characterize how neurological disorders affect this process, we aim to understand the normal mechanisms underlying the maturation of the function of the hippocampus, a structure playing a major role in learning and memory. Particularly, our goal is to determine how the ability of this structure to encode, store and retrieve information develops in immature rats. To do so, we will study the discharge of hippocampal neurons in developing, freely moving rats. These neurons, called place cells, are active only when the rat enters a specific region of the environment, the cell's place field. Place cells are believed to be the neuronal substrate of spatial memory. In a first Aim, we will evaluate place cell signal development in rats aged from postnatal day (P)18 to P60. Three experiments will investigate different aspects of place cell discharge. In the first experiment, the ontogeny of place cell signal quality and stability at short and long term will be analyzed. In the second experiment, we will determine how the sensory properties of place cells develop with age. The third experiment will focus on the relationships between place cell discharge and the hippocampal EEG oscillation called theta rhythm. This relationship, an example of temporal coding, is believed to be critical for organizing and processing information. Public Health Relevance: To determine the role of these maturational steps in learning and memory, we will study, in the second aim the relationships between place cell firing and memory performance in a spatial task. Place cells will be recorded in immature rats while they perform a place avoidance task. The eventuality of dissociation between spatial behavior and place cell firing will challenge our present understanding of hippocampal function. Our overall goal is to determine the critical phases of place cell development. This knowledge will serve as a reference for investigating how neurological disorders affect learning and memory systems. We believe that it will help define appropriate timing for clinical intervention in developmental disorders

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH086833-02
Application #
8035931
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
2010-04-01
Project End
2013-02-28
Budget Start
2011-03-01
Budget End
2013-02-28
Support Year
2
Fiscal Year
2011
Total Cost
$242,532
Indirect Cost
Name
Dartmouth College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
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Kleen, Jonathan K; Wu, Edie X; Holmes, Gregory L et al. (2011) Enhanced oscillatory activity in the hippocampal-prefrontal network is related to short-term memory function after early-life seizures. J Neurosci 31:15397-406
Scott, Rod C; Richard, Gregory R; Holmes, Gregory L et al. (2011) Maturational dynamics of hippocampal place cells in immature rats. Hippocampus 21:347-53