Metabotropic glutamate receptors in the vagal processing of taste information

描述（由申请人提供）：本提案中包含的研究计划的长期目标是阐明脑干回路在吞咽中的作用。迷走神经脑干复合体负责味觉相关的行为，如吞咽、对刺激的口腔排斥和呕吐。代谢型谷氨酸受体（mGluRs）在味觉相关信息传递中的作用尚未研究，但我们的初步证据表明，mGluR激活抑制迷走神经脑干复合体内的初级传入传递。mGluR激活还通过类似的机制抑制其他系统如脊髓和主动脉压力感受器中的活性。在功能上，mGluR介导的活性抑制可能是口腔刺激习惯化的基础，类似于mGluR如何调节嗅觉中对气味的习惯化或伤害感受中对疼痛刺激的习惯化。为了研究迷走神经脑干复合体中的mGluRs，我将利用药理学（mGluR激动剂和拮抗剂的应用）、膜片钳电生理学和分子（PCR，原位杂交）技术来确定mGluRs在迷走神经介导的味觉信息处理中的特定作用。我们的实验可能表明，mGluRs作为突触前自身受体的功能，以减少谷氨酸的释放。这可能提供了一种特定的机制，通过这种机制，对味觉刺激的习惯可能发生，这些结果可能扩展到两个主要领域。首先，迷走味觉系统在维持正常气道的呕吐反射中是重要的。第二，mGluR激动剂最近已显示出减少脂多糖诱导的厌食症。了解mGluR介导的习惯性口腔刺激在这些领域的每一个可能是至关重要的理解的条件。

DESCRIPTION (provided by applicant): The long-term objective of the research plan contained within this proposal is to elucidate the role of the brainstem circuitry in deglutition. The vagal brainstem complex is responsible for taste-related behaviors such as swallowing, the oral rejection of stimuli, and gagging. The role of metabotropic glutamate receptors (mGluRs) in the transmission of taste-related information has not yet been examined, but our preliminary evidence suggests that mGluR activation inhibits primary afferent transmission within the vagal brainstem complex. mGluR activation also inhibits activity in other systems such as the spinal cord and in aortic baroreceptors via a similar mechanism. Functionally, mGluR mediated inhibition of activity may underlie the habituation of oral stimuli, similar to how mGluRs modulate habituation to odors in olfaction or to painful stimuli in nociception. To study mGluRs in the vagal brainstem complex, I will utilize pharmacological (applications of mGluR agonists and antagonists), patch-clamp electrophysiology, and molecular (PCR, in situ hybridization) techniques to determine the specific role of mGluRs in the processing of vagally mediated taste information. Our experiments may suggest that mGluRs function as presynaptic autoreceptors to decrease the release of glutamate. This could provide a specific mechanism by which habituation to taste stimuli may occur, and these results could extend to two main areas. First, the vagal taste system is important in the gagging reflex for the maintenance of normal air passage. Second, mGluR agonists have recently been shown to decrease lipo-polysaccharide induced anorexia. The understanding of mGluR mediated habituation to oral stimuli in each of these areas may be critical to understanding the conditions.