Patricia M. Di Lorenzo - US grants

This proposal has been designed to approach the general question of how the brain encodes the palatability of a gustatory stimulus. Because decrebrate rats are capable of hedonic judgements about the tastants but are not capable of retaining conditioned taste aversions, it is probable that the brainstem alone is capable of encoding information about palatability, whereas more rostral neural structures may be necessary for modification of these judgements with experience. As a relay in the primary gustatory pathway which also has extensive projections to the forebrain, the parabrachial nucleus of the pons (PbN) may have a significant role in these processes. The three experiments proposed here are designed to: 1) investigate the changes in the electrical activity of the parabrachial nucleus of the pons (PbN) that correlate with the production of a conditioned taste aversion, and 2) investigate the interactions of forebrain mechanisms as they relate to the neural code for taste quality and palatability in the PbN. In three interrelated experiments, the character of the taste response in the PbN will be studied in flaxedilzed rats. In Experiment 1, alterations in the responses to each of the 4 basic tastes will be tested before and after they are paired with an intravenous injection of LiC1. In Experiment 2, the general influence of the forebrain on the conditioned changes in the PbN will be studied in the decrebrate rat under similar experimental conditions. Finally, Experiment 3 is designed to study the specific influence of the gustatory neocortex (known to have extensive reciprocal connections to the PbN) on the response characteristics and conditioned activity of single units in the PbN. This project has broad implications for the understanding of the etiology of eating and taste disorders.

DESCRIPTION (provided by applicant): This proposal is designed to study the neural coding of taste by learning about the circuitry of the first central synapse of taste-related nerves, the nucleus of the solitary tract (NTS). How the brain encodes taste is important because the coding mechanisms that are used by the taste system may also apply to other sensory systems. In addition, because of the link between taste and ingestion, the study of the taste system may provide insight into the etiology and/or treatment of eating disorders. Recent behavioral studies have suggested that the chorda tympani (CT) and the glossopharyngeal (GP), which innervate taste buds on the rostral 2/3 and caudal 1/3 of the tongue respectively, serve different functions in taste coding. At the present time, however, a description of the underlying circuitry in the central nervous system and of the functional interactions that support such a hypothesis is lacking. The long-term objective of the present proposal is to provide a description of the interaction of inputs onto taste cells in the NTS and the relationships of these inputs to the projection patterns of NTS cells. The specific aims are: 1) Evoked responses from electrical stimulation of the CT and GP nerves will be recorded in NTS cells and correlated with patterns of taste sensitivity. First, this experiment will test the hypothesis that the respective sensitivity patterns of the CT and GP nerves are conserved in the response profiles in NTS cells. Second, based on several suggestions in the literature, the hypothesis that input from the CT nerve inhibits input from the GP nerve will be tested using paired pulse electrical stimulation. 2) Evoked responses from electrical stimulation of the CT and GP nerve will be recorded in NTS cells, as well as evoked responses from electrical stimulation of the parabrachial nucleus of the pons (PbN), the second synapse in the ascending gustatory pathway. This experiment will test the hypothesis that the response profiles of NTS-PbN relay cells reflect parallel processing of taste stimuli by NTS cells receiving either CT or GP input. 3) Evoked responses from electrical stimulation of the CT and GP nerves and the gustatory neocortex (GN) will be recorded will be recorded in NTS cells. Taste responses in these cells will also be recorded before and after anesthetization of the ipsilateral and contralateral GN. This experiment will test the hypothesis that descending input from the GN differentially affects those cells that receive CT and GP input. By describing the taste responsivity of inputs and outputs of NTS cells, data from this project will help provide an understanding of information processing in the NTS.

[unreadable] DESCRIPTION (provided by applicant): An understanding of how taste stimuli are processed by the central nervous system (CMS) is important because the taste of food is a major determinant of ingestion. As such, it impacts the study of a variety of eating disorders including anorexia, bulimia and obesity. Of these, obesity looms large as a growing and costly societal problem in the United States that is nearing epidemic proportions. To further our understanding of taste processing, the present project is focused on the analysis of how temporal coding conveys information about taste stimuli in cells contained in the nucleus of the solitary tract (NTS), the first central relay in the taste system. HYPOTHESES are: 1) The temporal structure of a taste response in the NTS conveys information about taste stimuli, and 2) The temporal pattern of activity in an NTS taste response can evoke a taste-like sensation of predictable quality and hedonic value. SPECIFIC AIMS : 1) Information contributed by temporal coding will be quantified by analyses of the electrophysiological responses in the NTS of anesthetized rats to taste stimuli that vary in concentration and taste quality, and are presented in mixtures, and 2) Generalization of conditioned aversions to lick-contingent electrical stimulation of the NTS will be used to a) determine the critical features of the temporal pattern of electrical stimulation that are necessary and sufficient to evoke specific taste sensations and appropriate behavioral reactions, and b) construct a temporal sequence of electrical pulses which incorporates these critical features that, when used to drive activity in the NTS, will mimic the perceptual properties of a natural taste. SIGNIFICANCE: These experiments will provide data related to two aspects of temporal coding: the information conveyed by temporal patterns of responses and the function of a temporal code in taste perception. [unreadable] [unreadable]

Program Director/Principal Investigator: Savage, Lisa Project Summary: Binghamton University (BU) will continue our successful 20-yr affiliation with Monroe Community College (MCC), Onondaga Community College (OCC) and Westchester Community College (WCC) in the Upstate Bridges to the Baccalaureate Program. Our Bridges Program has under-represented (UR) student transfer (91%) and baccalaureate degree completion rates (84%) much greater the national (31.5% transfer rate; 46% degree completion) and New York State degree completion rates (60.2% overall and 38% for UR). Our long-term success is based on a partnership that successfully prepares UR students to take part in the biomedical educational and research enterprise (72% from 2007-2018; and the recent cycle from 2014 over 90%, of students earned baccalaureate STEM degrees). However, we believe that we can improve on our success with activities outlined in the following Aims: (1) To strengthen scientific literacy and promote confidence in scientific ability in early stage UR students. This is aimed at fostering persistence in biomedical science education and career choice. To enhance interest in careers in science, we will provide seminars at the CCs with a focus on science education and career awareness. We will also offer a Scientific Bootcamp at the beginning of our 8-wk Summer Research Experience to provide instruction on basic scientific skills and scientific rigor. In addition, the grant will fund supplementary math and science skills development at the CCs to improve UR students? science preparedness; (2) Provide an authentic, immersive, and rigorous research experience at BU to fortify commitment and enthusiasm for biomedical sciences. This will be accomplished by an 8-wk rigorous program of faculty-mentored summer research experience at BU; (3) We will promote advanced scientific education and professionalism as a way of reinforcing the proportion (currently 82%) of Bridges Scholars that obtain baccalaureate degrees in the biomedical and behavioral sciences. Bridges Scholars that transfer to BU will enroll in a Culture of Science course that includes instruction in Individual Development Plans, research ethics and communication of research. In addition, we fund research internships for a subset of Bridges Scholars during the academic year. The proposed program will promote the development of independent or honors research projects with research-active faculty mentors. We will also support travel to present independent research at discipline-specific international scientific conferences. The development of a strong science skill set and science career identity among UR students is critical for their continuation on the science career pathway.

? 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.