Role of Parabrachial Nucleus Benzodiazepines in Gustatory Coding and Behavior

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DESCRIPTION (provided by applicant): Obesity continues to be a major health concern affecting increasing numbers of Americans. Advances in the pharmacological treatment of obesity will dependent on a better understanding of the neural control and regulation of food palatability and consummatory behavior. Recent research has identified neuropeptide-Y and AGRP projections from the hypothalamus to the parabrachial nucleus (PBN) as important regulators of feeding behavior. These fibers coexpress GABA and knockout of GABA in these fibers profoundly reduces feeding and body weight. Prior studies showed that benzodiazepines (BZDs; GABAA receptor agonists) potently increase consumption by enhancing palatability, and a key site of their action may be the PBN. This proposal will clarify the role of BZDs in PBN gustatory functions. We will characterize BZD- induced changes in PBN neural gustatory coding and identify how these changes correspond with BZD-induced changes in behavioral measures of taste evaluation. Specifically, this proposal will employ a dual-pronged approach using parametrically matched behavioral and electrophysiological experiments. The behavioral experiments will characterize the dose- dependent effects of PBN infusions of BZDs on brief-access and long-term consummatory behavioral responses to varied intensities of tastants across all quality categories. We will evaluate whether an intraPBN injected BZD receptor antagonist blocks palatability responses to systemic BZD treatment to determine if the PBN is necessary for BZD-induced changes in consummatory patterns for tastants. The electrophysiological experiments will characterize the gustatory responses of PBN neurons prior to and after microapplication of BZDs directly on neurons within the nucleus. Based on preliminary data, we hypothesize that BZDs alter the gustatory neural coding within the PBN such that sweet responses increase and responses to sour and bitter stimuli are reduced, producing a narrowed tuning breadth. Our preliminary behavioral data predict changes in consumption of taste stimuli consistent with the changes in gustatory neural signaling such that licking to normally accepted tastants, such as sweets, and to normally avoided tastants, such as sour and bitter will be increased. The proposed studies should help to clarify the relative contributions of PBN GABA processing to the modulation of taste-guided behavior that possibly mediates intake modulatory signals from forebrain structures such as the hypothalamus. PUBLIC HEALTH RELEVANCE: Obesity, a primary national health concern, is due in large part to the overconsumption of highly palatable, energy dense foods. Development of pharmacological treatments to control obesity is dependent on understanding the neural systems that regulate the palatability of foods we consume. This proposal will identify specific neurochemical mechanisms in the brain involved in taste-mediated influences on food consumption.