A fundamental problem in the neurobiology of learning and memory is understanding the neural mechanisms of extinction. Behavior acquired as the result of Pavlovian conditioning can be extinguished by presenting the conditioned stimulus (CS) repeatedly without the unconditioned stimulus (US); this is known as the extinction effect. Although many neural activity studies of extinction imply that extinction is the reversal of acquisition, the behavioral phenomena of spontaneous recovery and disinhibition suggest that this is not the case and that extinction does not result in the loss or unlearning of the CS- US association in the brain. The behavioral training paradigm of Pavlovian conditioned suppression (conditioned emotional response, or CER procedure) will be used in all the proposed studies. The brain metabolic effects of extinction will be assessed with uptake of fluorodeoxyglucose (FDG). Metabolic responses from experimental rats will be compared to those of control rats exposed to the same tone to identify which regional activity changes occur in response to the tone conditioned stimulus (CS) after extinction of the CER. In addition, we will examine which of these brain metabolic activity changes are correlated with variations in the behavioral performance of each subject.
The specific aims are to use the FDG brain mapping technique to test three hypotheses: 1) The hypothesis that extinction is the opposite of acquisition, which predicts that extinction involves the loss of unlearning of the CS-US associative effects on the brain; 2) The hypothesis that extinction is similar to long-term habituation, which suggests that CS salience of the tone will be modulated in auditory and arousal systems; and 3) Pavlov s hypothesis that extinction is a form of inhibition of the conditioned response. Specifically, it is predicted that the CER extinction effect is due to the inhibition of the neural representation of the CS-CER association in the prefrontal cortex and central amygdala. In contrast, reversals of learning effects on other neural circuits are expected to be minor during extinction due to the savings of CS-US associative effects unrelated to CER inhibition. In the CER paradigm, a better understanding of extinction mechanisms may also have important clinical implications, such as the therapeutic use of extinction to reduce undesired conditioned fears.
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