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Aging and CA1 Neural Modeling of Trace Fear Conditioning

$70,250R03FY2001AGNIH

Pennsylvania State Univ Hershey Med Ctr, Hershey PA

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Abstract

This pilot study will address the Neural Research Objective and will examine the neural firing pattern of CA1-hippocampal neurons is aged rats performing a learning task called trace fear conditioning. Auditory trace fear conditioning is a learning task where animal are required to associate an auditory conditioned stimulus (CS) and a fear-producing shock-unconditioned stimulus (US) that are separated by a long empty 20- second trace interval. My work has shown that association of the CS and US in trace fear conditioning in young animals is dependent on cells in the dorsal hippocampus. Pilot data suggest that a proportion of aged rats (5 of 10) are impaired in the trace fear conditioning task. My most recent neurophysiological work has demonstrated that single neurons in the CA1-hippocampus of young animals show a very robust learning-related representation of the duration of the trace interval following trace fear conditioning. Specifically, on CS-alone trails following trace fear conditioning that CA1 neurons showed a time-locked firing pattern that represented the duration of the 20-second trace interval used on previous CS-trace-US trails. /there have been only a limited number of neurophysiological studies which have examined how aging affects the neuronal encoding of learning-related information. This is partly because it has been so difficult to describe neuronal patterns of activity in the young normal brain that confidently represent learned information. However, the robust neuronal representation of the trace interval obtained during trace fear conditioning should provide an excellent tool for determining if the CA1 neurons of aged animals show altered neuronal encoding of learning-related information. Therefore, this pilot study will examine the CA1-neuronal firing pattern of young and aged rats during trace feat conditioning. Rats of three different aged groups (4,21, and 26 months) will receive two trace fear conditioning sessions where each trail consists of an auditory tone-CS and a fear-producing shock-US which are separated by a very long 20-second trace interval. Single neurons will be recorded extracellularly from Ca1 during the trace fear conditioning task to determine if neurons in aged rats encode the duration of the trace interval, and to examine how the encoding o the trace interval is related to aging-related learning deficits. This work will provide important for later studies examining how other structures in the fear conditioning circuit (e.g., amygdala, dentate, entorhinal cortex) contribute to deficient encoding of information in the CA1 of aged animals.

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