Signals to Feed: Biological and Associative Mechanisms

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DESCRIPTION (provided by applicant): Disorders of memory function and of food intake regulation may seem to have little in common, except for the fact that both can have very negative effects on health and well-being. Yet, new data and new interpretations of older findings, suggest the existence of a number of intriguing links between the mechanisms that underlie learning and memory and the physiological processes involved with food intake regulation. The long-term goal of the proposed research is to understand how these processes are interrelated. Using a rat model, this work will focus on three neuropetides, insulin, leptin, and ghrelin, each of which have been proposed to provide information to the brain about the status of bodily energy resources, and each of which appears to be involved with the function of the hippocampus, a brain structure long considered to be an organ of learning and memory. In the initial phase of this research, behavioral paradigms will be used that can assess the extent to which these neuropeptides influence food intake regulation by (a) producing interoceptive hunger or satiety stimuli like those produced by periods of fasting or ad lib feeding; (b) altering the orosensory consequences of eating;(c) altering the post-ingestive after affects of eating and/or; (d) serving as predictive signals for when particular orosensory or post-ingestive consequences are likely to occur. Secondly, this research will use the role of the hippocampus in food intake regulation. The effects of selective neurotoxic lesions of the hippocampus on the learned and physiological controls of intake regulation will be evaluated. Thirdly, this research will begin to study systematically the possibility that processes involved with food intake regulation mediate the performance of hippocampal-dependent learning and memory functions. The goal of these experiments will be to determine if rats that have been made insulin-deficient or insulin-resistant show patterns of impairment on different learning and memory tasks that are like those shown by rats without a hippocampus. It is hoped that the research proposed here will enable us to identify common neural and associative bases for the control of learning and memory and food intake regulation. Discovery of how these mechanisms are interconnected should have important implications for understanding, diagnosing, and treating disorders of both memory and energy regulation.