Brainstem mechanisms controlling jaw movements

控制下颌运动的脑干机制

• 批准号: 6613255
• 负责人: SCOTT H CHANDLER
• 金额: $ 31.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6613255
• 关键词: biological signal transduction; brain stem; evoked potentials; excitatory aminoacid; glutamate receptor; interneurons; jaw movement; laboratory rat; mastication; membrane potentials; motor neurons; neural transmission; neuromuscular function; neurophysiology; neuroregulation; serotonin receptor; synapses; trigeminal nerve; video microscopy; voltage /patch clamp

DESCRIPTION (provided by applicant): The proper functioning of oral-facial motor systems is necessary for the survival of humans. The ingestive behaviors of mammals begins with suckling and progresses to drinking and chewing. Presently, there are very few studies addressing how the brain is organized to produce these behaviors. Even less is known about the etiology of various oral-motor disorders such as tardive dyskinesia, bruxism, and myofacial pain dysfunction syndromes. The long-term goals of this research are to understand both the mechanisms underlying the central nervous system control of normal jaw movements that occur during activities such as drinking and chewing, as well as the abnormal jaw movements that occur during various disorders. The specific aims of this proposal are to continue investigations, at the cellular level, into the neuronal mechanisms controlling trigeminal neuronal membrane excitability and burst discharge that are associated with the critical transition from primitive suckling behavior to adult-like mastication in the rat. We will combine whole cell patch clamp recording methods of neurons within the trigeminal nuclei responsible for oral-motor activity (mesencephalic V neurons and trigeminal interneurons) in brain slices with microstimulation, neurochemical, and mathematical modeling techniques to more fully elucidate 1) the mechanisms controlling excitability, and 2) the local chemical and electrical microcircuitry of these neurons. The project is divided into two Specific Aims. In Specific Aim I we will determine the locations of, and ionic mechanisms underlying, intrinsic burst generation in Mes V and trigeminal interneurons in the vicinity of the trigeminal motor nucleus and test the hypothesis that the underlying conductances are substrates for modulation by metabotropic glutamate receptor (mGluR) and serotonergic (5-HT) receptor activation. Specific Aim II focuses on characterizing the local excitatory and inhibitory chemical and electrical synaptic interactions that occur between distinct trigeminal neurons, and the modulation of these interactions by activation of mGluR and 5-HT receptors. The results of the proposed studies will provide insights into the local microcircuitry and the cellular mechanisms controlling discharge of distinct populations of trigeminal neurons involved in production of jaw movements at distinct developmental time points, and will serve as a cellular foundation for creation of neuronal models of masticatory rhythm and burst pattern generation.

描述（由申请人提供）：口面部运动系统的正常功能是人类生存所必需的。哺乳动物的摄食行为从吮吸开始，发展到饮水和咀嚼。目前，很少有研究涉及大脑如何组织产生这些行为。更少的是知道各种口腔运动障碍，如迟发性运动障碍，磨牙症，肌面疼痛功能障碍综合征的病因。这项研究的长期目标是了解中枢神经系统控制饮酒和咀嚼等活动期间正常下颌运动的机制，以及各种疾病期间发生的异常下颌运动。这个建议的具体目的是继续调查，在细胞水平上，控制三叉神经元膜兴奋性和爆发放电的神经机制，与大鼠从原始吸吮行为到成人样咀嚼的关键转变。我们将联合收割机全细胞膜片钳记录方法与微刺激、神经化学和数学建模技术相结合，在脑切片中记录三叉神经核内负责口腔运动活动的神经元（中脑V神经元和三叉神经中间神经元），以更全面地阐明1）控制兴奋性的机制，以及2）这些神经元的局部化学和电学微电路。该项目分为两个具体目标。在具体目标I中，我们将确定Mes V和三叉神经运动核附近的三叉神经中间神经元的内在爆发产生的位置和离子机制，并测试以下假设：基础电导是代谢型谷氨酸受体（mGluR）和多巴胺能（5-HT）受体激活的调制底物。具体目标II侧重于表征不同三叉神经元之间发生的局部兴奋性和抑制性化学和电突触相互作用，以及通过激活mGluR和5-HT受体调节这些相互作用。拟议的研究结果将提供深入了解当地的微电路和控制放电的不同群体的三叉神经元参与生产的下颌运动在不同的发展时间点的细胞机制，并将作为一个细胞的基础，为创造咀嚼节奏和突发模式的神经元模型的产生。