Functional Organization of the Central Gustatory System

描述（由申请人提供）：中枢味觉系统结构的损伤，例如岛叶和鳃盖（人类初级味觉皮层的部位），可以改变通过大脑的味觉相关信息的上升和下降流动，这很有可能破坏正常的味觉处理，并对健康和生活质量产生不利影响。随着在识别大脑中味觉反应神经元的药理学、连通性和生理表型方面取得更多进展，该领域在动物模型中开发和应用适当的行为测定以明确地将神经生物学过程与味觉功能联系起来变得越来越重要。文献中有证据表明，初级味觉皮层受损的患者表现出味觉减退，并且难以识别和识别味道。在大鼠中，味觉皮层的损伤会延迟（但不能消除）条件性味觉厌恶的获得，延迟基于味觉的预期对比的获得，并损害味觉恐惧症的表达。相反，这些损伤对无条件味觉偏好和回避的影响很小（如果有的话），并且不会破坏味觉偏好调节。文献中普遍的观点是，味觉皮层受损的动物表现出正常的味觉检测和辨别能力，但实际上，这仍有待明确测试。事实上，所有关于大鼠味觉皮层损伤影响的实验都涉及评估对味觉化合物的条件或非条件情感/享乐反应。此外，除了少数例外，味觉适口性是通过摄入和偏好测试来评估的，这些测试可能会受到食后因素的严重影响，并且只能提供情感反应的部分分析。因此，关于味觉皮层功能作用的结论是基于一组相对有限的行为观察。所提出的一系列实验的目标是通过明确测试味觉皮层在维持感觉辨别与情感味觉功能中的必要性来填补这一解释空白。使用技术先进的仪器（味觉计），我们计划在各种行为任务中测试有或没有鹅黄酸诱导的味觉皮层损伤的大鼠，这些任务旨在测量味觉敏感性（实验1）、味觉质量辨别（实验2和3）、条件性味觉厌恶的定性特异性（实验3）以及通过短暂舔舐测试（实验4）和口腔运动味觉反应性评估的对味觉刺激的无条件情感反应。 （实验 5）。我们预测这些病变将削弱敏感性并损害动物区分味觉刺激的能力，味觉刺激在心理物理任务中用作感觉信号，而不影响化合物的适口性。无论这些实验的具体结果如何，生成的数据都应该提供一个功能背景来理解中央味觉处理。 公共健康相关性：味觉受损可能会导致患者非常衰弱，对此类患者的生活质量产生不利影响并危及他们的健康。此外，考虑到味觉在进食和饮水中的作用，味觉系统的损害可能导致更复杂的临床疾病，包括营养状况、水矿物质平衡和肥胖。动物模型的开发可以通过实验操纵味觉系统并评估感知结果，这对于了解正常和异常味觉功能的潜在神经生物学至关重要——这是完善味觉脑部位损伤患者临床管理的第一步，并有可能导致治疗干预措施的发展。

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.