Neural Basis of Taste Elicited Ingestion and Rejection

描述（由申请方提供）：本提案的目的是确定啮齿动物后脑中的神经底物，味觉刺激通过该底物指导摄食行为。摄食行为的调节非常复杂，涉及中枢神经系统的广泛区域，但确定可口刺激和不可口刺激的基本味觉调节功能在尾脑干中完成。这些摄取和排斥的完成行为对于能量平衡的自我平衡控制是必不可少的。解剖学研究表明，延髓网状结构的外侧被盖区是一个多功能的基板，接受传入的感觉信号从孤束核的味觉区，并产生适当的orphinal模式的摄入或拒绝。当这一区域失活时，味觉引起的摄食和排斥反应就会消失。拟议的实验联合收割机几种技术来解决两个广泛的问题：脑干消费基板及其潜在机制的一般性和空间范围。通过药物输注到选定的前脑部位来增加对不同刺激的食欲反应，将与选定的脑干网状结构部位的可逆阻断相结合，以确定前脑信号是否会聚在单个后脑区域。第二个系列的微量输注研究将确定抑制性氨基酸和一氧化氮的作用orthodoniccoordination和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表达的立即早期基因c-fos产生的味觉刺激，以确定这些神经递质的来源和它们各自的受体在电路中的interneurons。诸如肥胖、高血压、神经性厌食症和吞咽困难等疾病都涉及消化功能障碍。了解摄取或拒绝食物的基本生物学决定的神经学基础将有助于这些慢性衰弱性疾病的最终解决方案。

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.