Date of Award

August 2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Psychology

First Advisor

James R. Moyer, Jr.

Committee Members

John M. Beggs, Fred J. Helmstetter, Devin Mueller, Rodney A. Swain

Keywords

Hippocampus, Intrinsic Excitability, Medial Prefrontal Cortex, Spine Density, Synaptic Plasticity, Trace Fear Conditioning and Extinction

Abstract

Pavlovian fear conditioning provides a useful model system for investigating the mechanisms underlying associative learning. In recent years, there has been an increasing interest in "trace" fear conditioning, which requires conscious awareness of the contingency of CS and US therefore considered as a rodent model of explicit fear. Acquisition of trace fear conditioning requires an intact hippocampus and medial prefrontal cortex (mPFC), but the underlying mechanisms are still unclear. The current set of studies investigated how trace fear conditioning affects neuronal plasticity in both hippocampus and mPFC in adult rats. Trace fear conditioning significantly enhanced both intrinsic excitability and synaptic plasticity (LTP) in hippocampal CA1 neurons. Interestingly, intrinsic excitability and synaptic plasticity were significantly correlated with behavioral performance, suggesting that these changes were learning-specific. The next set of experiments investigated learning-related changes in mPFC. In order to study circuit-specific changes, only neurons that project to the basolateral nucleus of amygdala (BLA) were studied by injecting a retrograde tracer into BLA. Trace fear conditioning significantly enhanced the excitability the layer 5 (L5) projection neurons in the infralimbic (IL) subregion of mPFC whereas it decreased the excitability of L5 projection neurons in the prelimbic (PL) subregion. In both IL and PL, the conditioning effect was time-dependent because it was not observed following a retention (tested 10 days after conditioning). Furthermore, extinction reversed the conditioning effect in both IL and PL, suggesting that these changes are transient and plastic. For comparison, the effects of delay fear conditioning on mPFC neuronal excitability was also studied. These data demonstrated that in adult rats delay fear conditioning significantly enhanced the intrinsic excitability of IL but not PL neurons. However, this conditioning effect was only significant in response to stronger (e.g., larger magnitude) current injections, suggesting that this learning effect was weak. Finally, how trace fear conditioning and extinction modulate dendritic spine density of mPFC-BLA projection neurons was also studied. These data suggest that the spine density is significantly higher in L2/3 neurons than that of L5 neurons, and that extinction facilitates the elimination of spines within L2/3 neurons in both IL and PL. Together these data implicate that both neurophysiological and morphological changes within hippocampus and mPFC are critical for the acquisition and extinction of trace fear conditioning in rats.

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