Neural Basis of Taste Elicited Ingestion and Rejection

描述（由申请人提供）：本提案的目的是确定啮齿动物后脑中的神经基质，通过这些神经基质，味觉刺激指导摄食行为。摄食行为的调节是极其复杂的，涉及中枢神经系统的广泛区域，但味觉决定美味和不美味刺激的基本调节功能是在尾侧脑干完成的。这些摄入和排斥的完善行为对能量平衡的稳态控制至关重要。解剖学研究表明，髓网状结构的外侧被盖区是一个多功能的基底，接收来自孤立束核的味觉区传入的感觉信号，并产生适当的摄入或排斥的运动模式。当这个区域在药理学上失活时，味觉引起的摄入和排斥反应就被消除了。提出的实验结合了几种技术来解决两个广泛的问题：脑干完善底物的普遍性和空间范围及其潜在机制。通过向选定的前脑部位注入药物，增加对不同刺激的食欲反应，并结合对选定的脑干网状结构部位的可逆阻断，以确定前脑信号是否会聚在一个单一的后脑区域。第二系列微输注研究将确定抑制性氨基酸和一氧化氮在运动性协调中的作用，相关的一系列研究将使用双标记免疫组织化学结合逆行运输和味觉刺激产生的即时早期基因c-fos的表达来确定这些神经递质的来源及其各自在回路中中间神经元上的受体。肥胖、高血压、神经性厌食症和吞咽困难等疾病都与消化功能障碍有关。了解摄入或拒绝食物的基本生物学决定的神经学基础将有助于最终解决这些慢性衰弱性疾病。

DESCRIPTION (provided by applicant): The objectives of this proposal are to determine neural substrates in the rodent hindbrain through which gustatory stimuli guide ingestive behavior. The regulation of ingestive behavior is exceedingly complex, involving widespread regions of the central nervous system but the basic regulatory function of taste to determine palatable from unpalatable stimuli is complete in the caudal brainstem. These consummatory behaviors of ingestion and rejection are essential to the homeostatic control of energy balance. Anatomical studies suggest that the lateral tegmental field of the medullary reticular formation is a multifunctional substrate, receiving afferent sensory signals from the gustatory region of the nucleus of the solitary tract and producing the appropriate oromotor patterns of ingestion or rejection. When this region is pharmacologically inactivated, taste-elicited ingestion and rejection reponses are eliminated. The proposed experiments combine several techniques to address two broad questions: the generality and spatial extent of the brainstem consummatory substrate and its underlying mechanisms. Increasing appetitive responses to different stimuli by pharmacological infusions into selected forebrain sites will be combined with reversible block of selected brainstem reticular formation sites to establish whether forebrain signals converge on a single hindbrain region. A second series of microinfusion studies will determine the role of inhibitory amino acids and nitric oxide on oromotor coordination and a related series of studies will use double-labeling immunohistochemistry combined with retrograde transport and expression of the immediate early gene c-fos produced by gustatory stimulation to identify the source of these neurotransmitters and their respective receptors on interneurons in the circuit. Diseases such as obesity, hypertension, anorexia nervosa and dysphagia all involve ingestive dysfunction. Understanding the neurological basis of the fundamental biological decision ingest or reject food will contribute to the eventual solution of these chronic debilitating disorders.