Functional Organization of the Central Gustatory System

中枢味觉系统的功能组织

• 批准号: 8077281
• 负责人: Alan C Spector
• 金额: $ 30.13万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8077281
• 关键词: Affect; Affective; Animal Model; Animals; Behavioral; Behavioral Assay; Brain; Clinical; Clinical Management; Complex; Data; Detection; Development; Discrimination; Disease; Equilibrium; Goals; Health; Human; Hypogeusia; Ibotenic Acid; Impairment; Injury; Insula of Reil; Intake; Lesion; Link; Literature; Location; Maintenance; Measures; Modality; Modeling; Molecular; Neurobiology; Neurons; Nutritional status; Obesity; Outcome; Pathway interactions; Patients; Pharmacology; Phenotype; Physiological; Population; Procedures; Process; Prosencephalon; Psychophysiology; Publishing; Quality of life; Rattus; Relative (related person); Rodent; Role; Sensory; Series; Signal Transduction; Site; Specificity; Stimulus; Structure; System; Taste Perception; Testing; Therapeutic Intervention; Vision; animal model development; base; behavior observation; conditioning; design; drinking; feeding; hedonic; infancy; parabrachial nucleus; preference; public health relevance; research study

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.

描述（由申请人提供）：对中枢味觉系统中的结构（例如，人的初级味觉皮层的部位）的损伤，可以改变通过大脑的上升和下降的味觉相关信息的流动，这很可能会破坏正常的味觉处理，并可能对健康和生活质量产生有害后果。随着在辨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进展，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对于该领域变得越来越重要。文献中有证据表明，涉及初级味觉皮层损伤的患者表现出味觉减退，难以识别和识别味觉。在大鼠中，味觉皮层的病变延迟，但不消除，收购的条件性味觉厌恶，延迟收购的味觉为基础的预期对比，并损害表达的味觉新恐惧症。与此相反，这些病变引起的影响很小，如果有的话，对无条件的味觉偏好和回避，不破坏味觉偏好条件。在文献中流行的观点是，味觉皮层病变的动物显示正常的味觉检测和辨别能力，但在现实中，这仍然是明确的测试。几乎所有的实验对大鼠的味觉皮层病变的影响都涉及评估条件或非条件的情感/享乐反应的味道化合物。此外，除了少数例外，已经用摄入和偏好测试评估了味道的适口性，这可能受到摄入后因素的严重影响，并且仅提供了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受限的行为观察。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种解释性空白。使用技术复杂的设备（味觉计），我们计划在各种行为任务中测试在味觉皮层中有和没有鹅膏蕈氨酸诱导的损伤的大鼠，这些行为任务旨在测量味觉敏感性（实验1）。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2和3）。3），和无条件的情感反应的味觉刺激评估的简短访问舔测试（实验。4)和味觉反应性（Exp.（五）。我们预测，这些病变将钝的敏感性和妥协的动物的能力，区分味觉刺激，用作感官信号的心理物理任务，而不影响适口性的化合物。无论这些实验的具体结果如何，所产生的数据都应该提供一个理解中枢味觉处理的功能背景。 公共卫生相关性：味觉的损伤可能非常虚弱，对这些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水中的作用，味觉系统的损伤可能会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，其中味觉系统可以实验操作和评估的感知后果，是必不可少的获得正常和异常味觉功能的基础神经生物学的理解-在完善的患者的临床管理味觉大脑部位受损，并可能导致治疗干预措施的发展的第一步。