Functional Organization of the Central Gustatory System

描述(申请人提供)：损伤中央味觉系统的结构，如岛和盖，人类初级味觉皮质的位置，可以改变大脑中与味觉相关的上行和下行信息流，这可能极大地扰乱正常的味觉处理，并可能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、连接性和生理表型方面取得更多的进展，该领域开发和应用适当的动物模型中的行为分析来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，初级味觉皮质受损的患者表现出味觉减退，并难以识别和识别味道。在大鼠中，味觉皮质的病变延缓了条件味觉厌恶的获得，延缓了基于味觉的预期对比的获得，并损害了味觉新恐惧症的表达。相比之下，这些损伤几乎不会对无条件的味觉偏好和回避产生影响，也不会扰乱味觉偏好的条件反射。文献中的主流观点是，有味觉皮质损伤的动物表现出正常的味觉检测和辨别能力，但实际上，这一点仍有待明确测试。几乎所有关于大鼠味觉皮质损伤影响的实验都涉及到对味觉化合物的条件或非条件情感/享乐反应的评估。此外，除了少数例外，味觉适口性的评估是通过摄入量和偏好测试进行的，这些测试可能会受到摄入后因素的严重影响，并且只能提供对情感反应的部分分析。因此，关于味觉皮质的功能作用的结论是基于一组相对有限的行为观察。拟议中的一系列实验的目的是通过明确测试味觉皮质在维持感觉-辨别与情感味觉功能中的必要性来填补这一解释空白。使用一种技术先进的仪器(Gustometer)，我们计划在各种旨在测量味觉敏感度的行为任务中测试有和没有鹅掌酸诱导的味觉皮质损伤的大鼠。1)、味质辨别(Exp2&3)、条件性味觉厌恶的定性特异性(Exp.3)，以及通过简单的接近舔试验(Exp.4)和运动味觉反应(Exp.5)。我们预测，这些病变将钝化敏感性，损害动物区分在心理物理任务中用作感觉信号的味道刺激的能力，而不会影响化合物的适口性。不管这些实验的具体结果如何，产生的数据应该提供一个功能上下文，在其中理解中央味觉处理。 与公共卫生相关：味觉受损可能会使人非常虚弱，对这类患者的生活质量产生不利影响，并危及他们的健康。此外，鉴于味觉在进食和饮用中的作用，味觉系统的损害可能会导致更复杂的临床疾病，涉及营养状况、水矿物平衡和肥胖。在动物模型中，味觉系统可以进行实验操作并评估感知后果，这对于理解味觉功能正常和异常的潜在神经生物学至关重要--这是完善味觉大脑部位受损患者临床治疗的第一步，并可能导致治疗干预措施的开发。

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.