Parabrachial-Forebrain Interactions in CTA

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DESCRIPTION (provided by applicant): The long term goal of the current proposal is to determine the neural substrates of conditioned taste aversion (CTA), a profoundly important learning mechanism that protects against the repeated ingestion of toxic food. Evolution has predisposed animals (including humans) to associate gastrointestinal malaise (termed the unconditioned stimulus or US) with the taste of the food (the conditioned stimulus or CS). So powerful is this mechanism that cancer patients (despite the fact that they are fully aware that the food did not cause the illness) may develop strong aversions to their diets (leading to a loss of appetite and anorexia) because the adverse visceral side effects of chemotherapy are nonetheless associated with the foods they consumed before treatment. Similarly, animals rendered comatose following consumption of food nevertheless display a CTA if they survive the poisoning. These and related findings emphasize the importance of brainstem nuclei in the development of CTAs. We have helped identify the medial parabrachial nucleus (MPBN) as a fundamentally important area for the acquisition of CTA. We consider that the MPBN is critically involved in the associative mechanism that links the taste CS with the aversive US. However, the finding that chronic precollicular decerebrations (which disconnect the brainstem from the forebrain while leaving the MPBN intact) also prevent the acquisition of CTA, indicates that the MPBN does not work alone: CTA acquisition depends upon an interplay between the MPBN and forebrain structures. Thus, the present proposal seeks answers to the following questions: (1) which forebrain structures interact with the MPBN during CTA acquisition and (2) what is the nature of that interaction? Specific Aim 1 will address the first question by focusing on five brain regions that are connected with the MPBN and, in most cases, have been implicated in some aspect of CTA: the basolateral arnygdala, central nucleus of the amygdala, insular cortex, lateral hypothalamus and the bed nucleus of the stria terminalis. To determine the nature of the MPBN-forebrain interactions, Specific Aims 2 and 3 will employ tasks that have previously proven successful in identifying the role of the MPBN in CTA. By studying the behavioral breakdowns consequent to excitotoxic lesions of structures connected with the MPBN, we expect to make significant progress in our long-term goal of defining the neural system responsible for CTA acquisition.