Brainstem mechanisms controlling jaw movements

描述（由申请人提供）：口腔-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哺乳开始，逐渐发展到喝水和咀嚼。目前，很少有研究表明大脑是如何组织产生这些行为的。关于各种口腔运动障碍的病因，如迟发性运动障碍、磨牙症和肌面疼痛功能障碍综合征，我们所知的就更少了。这项研究的长期目标是了解中枢神经系统控制正常颌骨运动的机制，这些运动发生在诸如饮酒和咀嚼等活动中，以及在各种疾病中发生的异常颌骨运动。本研究的具体目标是在细胞水平上继续研究控制三叉神经膜兴奋性和突发放电的神经元机制，这些机制与大鼠从原始哺乳行为到成人咀嚼行为的关键转变有关。我们将把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）的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，以更充分地阐明1)控制兴奋性的机制，以及2)这些神经元的局部化学和电微电路。该项目分为两个具体目标。在Specific Aim I中，我们将确定三叉神经运动核附近的Mes V和三叉神经中间神经元的内在脉冲产生的位置和潜在的离子机制，并测试潜在的电导是代谢性谷氨酸受体（mGluR）和5-羟色胺能（5-HT）受体激活调节的底物的假设。特异性目的II侧重于描述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受体对这些相互作用的调节。所提出的研究结果将提供局部微电路和细胞机制的见解，以控制在不同发育时间点参与颌骨运动产生的三叉神经细胞的不同种群的放电，并将作为创建咀嚼节奏和爆发模式产生的神经元模型的细胞基础。

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.