Neural Basis of Taste Elicited Ingestion and Rejection

描述(申请人提供)：这项建议的目标是确定啮齿动物后脑中的神经底物，味觉刺激通过这些底物来指导摄食行为。对摄食行为的调节极其复杂，涉及中枢神经系统的广泛区域，但味觉的基本调节功能在尾侧脑干完成，以确定是否可口。这些摄取和排斥的消耗行为对于能量平衡的动态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种多功能底物，接收来自孤束核味觉区域的传入感觉信号，并产生适当的摄取或排斥运动模式。当这个区域被药物灭活时，味觉诱导的摄取和排斥反应就会消除。拟议的实验结合了几种技术来解决两个广泛的问题：脑干损毁底物的普遍性和空间范围及其潜在的机制。通过向选定的前脑部位注入药物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性阻断相结合，以确定前脑信号是否会聚在单一的后脑区域。第二系列微量输注研究将确定抑制性氨基酸和一氧化氮在口腔运动协调中的作用，相关系列研究将使用双标记免疫组织化学结合味觉刺激产生的即刻早期基因c-fos的逆行运输和表达，以确定这些神经递质的来源及其各自在回路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进食功能障碍有关。了解摄取或拒绝食物这一基本生物决定的神经学基础将有助于这些慢性衰弱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.