Functional Organization of the Central Gustatory System

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Injury to structures in the central gustatory system such as the insula and operculum, the site of primary gustatory cortex in humans, can alter the flow of ascending and descending taste-related information through the brain which has great potential to disrupt normal gustatory processing and can have detrimental consequences on health and quality of life. As more advances are made in discerning the pharmacology, connectivity, and physiological phenotype of taste-responsive neurons in the brain, it is becoming increasingly critical for the field to develop and apply appropriate behavioral assays in animal models to explicitly link neurobiological processes to taste function. There is evidence in the literature that patients with damage involving primary gustatory cortex display hypogeusia and have difficulty identifying and recognizing tastes. In rats, lesions in the gustatory cortex retard, but do not eliminate, the acquisition of a conditioned taste aversion, retard acquisition of taste-based anticipatory contrast, and impair the expression of taste neophobia. In contrast, these lesions cause little, if any, effect on unconditioned taste preference and avoidance and do not disrupt taste preference conditioning. The prevailing view in the literature is that animals with gustatory cortex lesions display normal taste detection and discriminability, but, in actuality, this remains to be explicitly tested. Virtually all of the experiments on the effects of gustatory cortex lesions in rats have involved assessment of either conditioned or unconditioned affective/hedonic responsiveness to taste compounds. Moreover, with few exceptions, taste palatability has been assessed with intake and preference tests, which can be heavily influenced by postingestive factors and provide only a partial analysis of affective responsiveness. Thus, conclusions regarding the functional role of gustatory cortex are based on a relatively constrained set of behavioral observations. The goal of the proposed series of experiments is to fill this interpretive void by explicitly testing the necessity of the gustatory cortex in the maintenance of sensory-discriminative vs. affective taste function. Using a technically sophisticated apparatus (gustometer), we plan to test rats with and without ibotenic acid-induced lesions in the gustatory cortex in a variety of behavioral tasks designed to measure taste sensitivity (Exp. 1), taste quality discrimination (Exp.2 & 3), the qualitative specificity of conditioned taste aversions (Exp. 3), and unconditioned affective responsiveness to taste stimuli as assessed by brief access licking tests (Exp. 4) and oromotor taste reactivity (Exp. 5). We predict that these lesions will blunt sensitivity and compromise the animal's ability to discriminate among taste stimuli that are used as sensory signals in psychophysical tasks, without affecting the palatability of the compounds. Regardless of the specific outcomes of these experiments, the data generated should provide a functional context in which to understand central gustatory processing. PUBLIC HEALTH RELEVANCE: Impairments in the sense of taste can be very debilitating, adversely affecting the quality of life in such patients and jeopardizing their health. Moreover, given the role of taste in feeding and drinking, damage to the gustatory system can potentially contribute to more complex clinical disorders involving nutritional status, hydromineral balance, and obesity. The development of animal models, in which the gustatory system can be experimentally manipulated and the perceptual consequences assessed, is essential to gain an understanding of the underlying neurobiology of normal and abnormal taste function - a first step in refining the clinical management of patients suffering damage to gustatory brain sites and potentially leading to the development of therapeutic interventions.