Vagal Influence on Brainstem Plasticity and Neural Coding of Taste

University Of Georgia, Athens GA

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Abstract

? DESCRIPTION (provided by applicant): Roux-en-Y gastric bypass (RYGB) is the most effective method to achieve major, long-term weight loss. Patients who have undergone RYGB often report an aversion to calorie-dense foods. However, mechanisms underlying the effects of RYGB on taste alterations are incompletely understood. Our long-term goal is to understand the neural mechanisms that determine taste alterations following diet-induced obesity (DIO) and RYGB. Specifically, we want to detail the neuroanatomical, neurochemical and neurophysiological sequelae of reorganization of subdiaphragmatic vagal afferents, resulting from obesity and following RYGB, as they relate to gustatory signaling in nucleus of the solitary tract (NTS). Our central hypothesis is that damage to the gastric branches of the vagus, a consequence of RYGB, induces synaptic plasticity and circuit reorganization in the intermediate (feeding) and rostral (gustatory) NTS. Considering the NTS integrates both gustatory and gastrointestinal afferent information, we predict these changes in primary visceral afferent signaling fundamentally change how information about taste is encoded. Our central hypothesis will be tested by achieving the following specific aims: Specific Aim 1: Test the hypothesis that gastric vagotomy (VGX) and RYGB surgery induce reorganization and synaptic plasticity in the rostral NTS via transient withdrawal of central vagal afferent terminals from the caudal and intermediate NTS. Changes in vagal innervation will be investigated at the morphological and functional levels using a combination of anterograde tracers, synapse specific markers and patch-clamp electrophysiology in horizontal brain sections. We expect that, because of the known caudal-to-rostral projections within the NTS, the weakened vagal input experienced by DIO and further altered by RYGB will be reflected in subtle alterations in glutamate release and efficacy in the NTS. Specific Aim 2: Using electrophysiological recordings from the NTS of awake rats, we will test the hypothesis that obesity, gastric VGX and RYGB selectively modify taste-related intranuclear communication and that this effect will be reflected in the taste-evoked responses among NTS neurons. Analyses will focus on quantifying functional connections among ensembles of simultaneously recorded NTS cells as well as determining the information contributed by rate and temporal coding in taste-evoked responses. The proposed work is innovative because it connects the role of vagus nerve damage-induced plasticity within the NTS with taste alterations following DIO and RYGB. Results, of the proposed project, will provide a deeper understanding of the effects of obesity and RYGB on the neural circuitry underlying gustatory signaling in the brainstem. This knowledge will enable more systematic and targeted manipulations, aimed at revealing mechanisms by which RYGB reduces consumption of high-caloric foods and advance the development of novel surgical and non-surgical therapeutic interventions, to promote effective weight loss.