Acute and Chronic Microdialysis in the Gustatory System

描述(申请人提供)：我们建议在 作为研究氨基酸的一种技术的清醒、行为准备 大鼠吻侧味觉反应核内的递质和神经肽 孤束(RNST)。虽然微渗析已经在许多地区使用 在取得巨大成功的CNS中，这种技术的潜力仍然存在 在味觉系统中未被开发。缺盐、饥饿、饱腹感和 条件性厌恶都已被证明会影响神经反应 在味觉系统中。这些依赖于状态的变化的神经基础是 未知，但根据它们在其他感觉系统中的作用，占主导地位 对于多肽神经调节剂，可能是通过中间神经元利用 兴奋性或抑制性氨基酸，是一个令人信服的假说。理解 味觉加工的功能神经化学将极大地 通过监控多种神经活性物质的释放来促进 在一只积极从事味觉驱动行为的动物身上。微透析罐 满足这些要求。本研究将为以下工作提供基础 通过建立微透析的能力来评估这一假说 一级味觉的高效液相色谱和电化学检测 接力赛。第一个实验将监测麻醉剂中氨基酸的释放。 制备，其中可以精确地控制味觉刺激。这个 这些实验的结果将对解释在一个 将应用微透析监测氨基酸的第二系列研究 在清醒的准备中释放。第三系列研究将会展开。 改良式微透析评价多种神经肽的释放 为此目的的电化学检测技术。当拟议的研究 都取得了成果，未来的工作将集中在研究 味觉敏感度波动的神经化学基础 新陈代谢或营养状况，以及作为学习或任务要求的功能。 与味觉相关的动态神经化学特征 在不同的动态平衡条件下进行加工提供了治疗途径 要么增加食物摄入量以应对恶病质，要么限制食物摄入量 肥胖。

DESCRIPTION (provided by applicant): We propose to establish microdialysis in the awake, behaving preparation as a technique for investigating amino acid transmitters and neuropeptides in the gustatory-responsive (rostral) nucleus of the solitary tract (rNST). Although microdialysis has been used in many regions of the CNS with great success, the potential of this technique has remained unexploited in the gustatory system. Salt deprivation, hunger, satiety and conditioned aversions have all been demonstrated to impact neural responsiveness in the gustatory system. The neural basis for these state-dependent changes is unknown, but, based on their role in other sensory systems, a predominant role for peptide neuromodulators, perhaps acting via interneurons utilizing excitatory or inhibitory amino acids, is a compelling hypothesis. Understanding the functional neurochemistry of gustatory processing would be greatly facilitated by the ability to monitor the release of multiple neuroactive agents in an animal actively engaged in gustatory-driven behavior. Microdialysis can meet these requirements. The present studies will provide a foundation for assessing this hypothesis by establishing the capabilities of microdialysis followed by HPLC and electrochemical detection in the first-order gustatory relay. The first experiments will monitor amino acid release in an anesthetized preparation, in which precisely controlled taste stimulation is possible. The results of these experiments will be critical in interpreting data obtained in a second series of studies which will apply microdialysis to monitor amino acid release in an awake preparation. A third series of studies will develop microdialysis for assessing the release of multiple neuropeptides, by adapting electrochemical detection techniques to this purpose. When the proposed studies are brought to fruition, future work will be directed at examining the neurochemical basis for fluctuations in gustatory sensitivity as a function of metabolic or nutritional status, and as a function of learning or task demands. The characterization of the dynamic neurochemistry associated with gustatory processing under varying homeostatic conditions offers therapeutic avenues to either increase food intake in response to cachexia or to limit intake for obesity.