Metabotropic glutamate receptors in the vagal processing of taste information

味觉信息迷走神经处理中的代谢型谷氨酸受体

• 批准号: 7409386
• 负责人: Robert M Hallock
• 金额: $ 5.05万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2009-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7409386
• 关键词: 2-amino-4-phosphono-propinate; Agonist; Air; Amino Acids; Anorexia; Applications Grants; Area; Autoreceptors; Axon; Behavior; Binding; Brain; Brain Stem; Cell Nucleus; Cell Size; Cells; Chromosome Pairing; Complex; Complex Mixtures; Condition; Deglutition; Developmental Cell Biology; Electrophysiology (science); Fiber; Fingers; Food; Gagging; Ganglia; Glutamate Receptor; Glutamates; Goals; Goldfish; In Situ Hybridization; In Vitro; Interneurons; Kainic Acid Receptors; Lobe; Maintenance; Mammals; Mediating; Mentors; Messenger RNA; Metabotropic Glutamate Receptors; Methods; Modeling; Molecular; Motor; Myxoid cyst; N-Methylaspartate; Neuraxis; Neurons; Neurotransmitters; Nociception; Nucleus solitarius; Odors; Oral; Oral cavity; Pain; Physiologic pulse; Polymerase Chain Reaction; Polysaccharides; Pressoreceptors; Presynaptic Receptors; Process; Pulse taking; Reflex action; Research; Rodent Model; Role; Sensory; Slice; Smell Perception; Spinal Cord; Stimulus; Sum; Synapses; Synaptic Transmission; System; Taste Perception; Techniques; Testing; Vertebrates; Visceral; afferent nerve; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; amino 3 hydroxy 5 methylisoxazole 4 propionate; experience; extracellular; ganglion cell; metabotropic glutamate receptor 4; neurotransmission; patch clamp; postsynaptic; presynaptic; professor; receptor function; research study; response; transmission process

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.

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与味觉相关的行为，如吞咽、口头拒绝刺激和呕吐。代谢型谷氨酸受体(MGluRs)在味觉相关信息传递中的作用尚未被研究，但我们的初步证据表明，mGluR的激活抑制了迷走神经脑干复合体内的初级传入传递。MGluR的激活也通过类似的机制抑制其他系统的活动，如脊髓和主动脉压力感受器。在功能上，mGluR介导的活动抑制可能是口腔刺激习惯化的基础，类似于mGluR调节嗅觉中的气味或伤害性刺激中的疼痛刺激的习惯化。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(聚合酶链式反应、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殊作用。我们的实验可能表明，mGluRs可能作为突触前自身受体来减少谷氨酸的释放。这可能提供了一种特定的机制，通过这种机制可以发生对味觉刺激的习惯性反应，这些结果可能扩展到两个主要领域。首先，迷走神经的味觉系统在维持正常呼吸道的呕吐反射中起着重要作用。第二，mGluR激动剂最近被证明可以减轻脂多糖引起的厌食症。对mGluR介导的口述刺激习惯化的理解可能是理解这些情况的关键。