Conditioned taste aversion (CTA) is a form of associative learning in which an animal avoids and reacts aversively to the taste of a food that has previously been paired with illness. CTA has been described in many species, from invertebrates to humans, and has important implications in drug and radiation therapies. It is also a model for altered responsiveness in ingestive behaviors, as in eating disorders. We have discovered that the induction of the immediate-early gene c-Fos by intraoral infusion of sucrose in the medial intermediate region of the nucleus of the solitary tract (iNTS) and the central nucleus of the amygdala (CeA) in the rat appears to be a specific and quantifiable neuronal correlate of the expression of a CTA previously acquired by pairing intraoral infusions of sucrose with lithium chloride. We hypothesize that cFos expression reveals functionally important brain sites mediating CTA, and that the time course of CTA consolidation and c-Fos expression in some of these sites reveals the time and place of gene expression that mediates CTA learning. We will make fiber-sparing, excitotoxic lesions of brain sites that express c-Fos after CTA acquisition and expression. Alterations in CTA induced by lesions will be measured by quantifying intake, taste reactivity, and c-Fos expression. We will quantify the time course of consolidation of long-term CTA memory, and determine the critical period of gene expression required for consolidation with site-specific injections of protein synthesis inhibitors. We will then use single-cell antisense RNA amplification to identify the neurochemical phenotype and gene expression profile of c- Fos-positive cells in critical brain sites at critical times of consolidation. This proposal presents a novel approach to CTA by correlating the effects of fiber-sparing lesions on behavior with effects on the pattern of c-Fos expression, and by examining molecular correlates of the transition from short-term to long-term memory in CTA learning. These experiments will contribute to an understanding of the neural pathways and molecular mechanisms underlying changes in food preferences that occur in eating disorders such as obesity and anorexia nervosa.
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