BRAIN STEM MECHANISMS CONTROLLING JAW MOVEMENT

这项提议的具体目的是进一步描绘神经元 控制下颌节律性运动(RJM)的机制 豚鼠的咀嚼。我们将结合电生理学， 神经解剖学和神经药理学技术来定义 脑干回路及其潜在机制负责 刺激咀嚼引起的下颌节律性运动 大脑皮层。我们建议1)确定特定的神经信使的作用 短脉冲时三叉神经前运动神经元兴奋性的控制 训练皮质刺激或在重复皮质诱导的RJM期间 刺激。2)确定已确认的三叉神经的位置(S) 含有谷氨酸、5-羟色胺或去甲肾上腺素的前运动神经元，以及 3)确定三叉神经前运动神经元的哪些亚群 咀嚼皮质皮质分离皮质传入的特异性靶点。 该项目分为两个主要部分。在第一部分，单个单元格 将利用记录和微离子电泳法喷射技术 确定特定神经信使在对照中的重要性 皮质诱发RJMS时三叉神经前运动神经元的兴奋性。 在皮质诱发的RJMS期间，将记录已识别的前运动神经元 同时应用假定的神经信使激动剂和 对抗者。第二部分将重点介绍利用神经解剖学和 免疫组织化学技术进一步表征BMP的作用 RJM产生中的三叉神经前运动神经元。在第一组 实验中，我们将结合免疫组织化学技术 用逆行示踪技术识别神经递质 白纹伊蚊亚群三叉神经节前神经元的定位 含有下列神经信使的前运动神经元：谷氨酸， 血清素和去甲肾上腺素。在第二系列实验中， 将进行标记实验以确定亚群 特异性接受皮质激素输入的三叉神经前运动神经元 来自咀嚼皮质。 这项研究的长期目标是了解这两种机制 正常节律颌骨的中枢神经系统控制 运动在诸如喂食和饮水等活动中发生的运动，如 以及不正常的。不由自主的下巴运动在紊乱中发生 如迟发性运动障碍、磨牙症和肌筋膜疼痛功能障碍 综合症。这些异常颌骨运动产生的原因 尚不清楚，尽管磨牙症被认为与压力有关，而且 迟发性运动障碍导致基底节区多巴胺活动中断 神经节。建议在豚鼠身上进行的实验结果将 提供对神经生理学和药理学的见解 机制，以及脑干水平的解剖基础， 无意识节律性下颌运动产生的潜在原因 人类。

The specific aims of this proposal are to further delineate the neuronal mechanisms controlling rhythmical jaw movements (RJMs) resembling mastication in the guinea pig. We will combine electrophysiological, neuroanatomical, and neuropharmacological techniques to define the brainstem circuits and their underlying mechanisms responsible for rhythmical jaw movements induced by stimulation of the masticatory cortex. We propose to 1) determine the role of specific neuromessengers in controlling trigeminal premotoneuronal excitability during short pulse train cortical stimulation or during RJMs induced by repetitive cortical stimulation. 2) establish the location(s) of identified trigeminal premotoneurons which contain glutamate, serotonin, or norepinephrine, and 3) determine which subpopulation of trigeminal premotoneurons are specific targets of corticofugal afferents arising in masticatory cortex. The project is divided into two main parts. In part I, single cell recording and microiontophoretic ejection techniques will be utilized to determine the importance of specific neuromessengers in the control trigeminal premotoneuronal excitability during cortically induced RJMs. Identified premotoneurons will be recorded during cortically induced RJMs while simultaneously applying putative neuromessenger agonists and antagonists. Part II will focus on utilizing neuroanatomical and immunohistochemical techniques to further characterize the roles of trigeminal premotoneurons in RJM production. In the first set of experiments, we will combine immunohistochemical techniques for neurotransmitter identification with retrograde tracer techniques for trigeminal premontoneuronal localization of subpopulations of premotoneurons which contain the following neuromessengers: glutamate, serotonin, and norepinephrine. In the second series of experiments double labelling experiments will be performed to determine the subpopulation of trigeminal premotoneurons which specifically receive corticofugal input from masticatory cortex. The long-term goal of this research is to understand both the mechanism underlying the central nervous system control of normal rhythmic jaw movements that occur during activities such as feeding and drinking, as well as the abnormal. Involuntary, jaw movements occurring in disorders such as tardive dyskinesia, bruxism and myofascial pain dysfunction syndrome. The etiology of the generation of these abnormal jaw movements is unknown, although bruxism is thought to be related to stress, and tardive dyskinesia to a disruption of dopamine activity in the basal ganglia. The results of the proposed experiments in the guinea pig will provide insights into the neurophysiological and pharmacological mechanisms, as well as anatomical substrates at the brainstem level, underlying the production of involuntary rhythmic jaw movements in humans.