: Broad, long-term objective: To determine the neural substrate of the learning and extinction of a conditioned aversion. Evidence suggests that the expression of c-Fos produced by the immediate-early gene (lEG) c-fos may not only mediate sensory experience but may also be instrumental in the formation of conditioned taste aversions (CTAs). The proposed work combines behavioral and immunohistochemical techniques in order to explore the role of this LEG in learning and extinction. Background: While a great deal of effort has gone into discovering the means by which the brain remembers new information, relatively little work has addressed the processes by which the brain discards or discounts less useful data. It is uncertain whether the process of extinction represents an """"""""unlearning"""""""" of material or if it is an acquisition of new information suggesting that the old material, while retained, is no longer useful and should therefore be ignored. There is empirical evidence on both sides of this issue. Methods and Objectives: We will create CTAs in rats by pairing the taste of saccharin (SAC; CS) with an i.p. injection of Lithium Chloride (L1C1; US). Later, some animals will receive extinction trials (i.e., given access to the SAC solution without the LiC1). Additional conditioned, yoked controls and explicitly unpaired CS-US yoked controls will not receive extinction trials. When subjects in the CTA/extinction group have reach pre-specified criterion of saccharin consumption, these subjects and their yoked controls will be perfused and their brains prepared for c-Fos immunohistochemistry. The objectives of the proposed work include: (1) Identifying brain areas important in the acquisition and extinction of a CTA as well as in the sensation of the CS and US; (2) Documenting the relationship between CTA acquisition/extinction and c-Fos protein expression in the brain; (3) Discovering the dynamic changes in neural activity that accompany the stages of extinction; and (4) Gaining insights into whether CTA extinction is a """"""""forgetting"""""""" of information (i.e., fading of memory CS = illness), a """"""""reversal"""""""" of conditioning (i.e., unlearning of CS = illness) or the acquisition of additional information (i.e., CS = safety in certain contexts). Will extinction of the CTA reverse the pattern of c-fos expression seen in conditioned animals? Alternatively, will the brain nuclei originally expressing c-fos continue to do so? What additional brain areas become active during different stages of extinction? What is the correlation between behavioral indicators of learning/extinction and c-fos expression in various brain nuclei known to be involved in CTA memory? Health relatedness: This project will reveal some of the neural mechanisms of learning and memory and therefore will advance the development of treatments for various neurological disorders, deficits in extinction (e.g., posttraumatic stress disorder) and conditioned aversions associated with cancers.
