Determining Functions of a Brainstem Pre-motor Module In Masticatory Jaw Movement

确定脑干前运动模块在咀嚼颌运动中的功能

• 批准号: 8649185
• 负责人: Edward John Stanek
• 金额: $ 3.33万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8649185
• 关键词: Adult; Area; Attenuated; Axon; Behavior; Behavioral; Brain Stem; Bruxism; Cell Nucleus; Chronic; Complex; Deglutition; Development; Disease; Dystonia; Electric Stimulation; Electrodes; Electrophysiology (science); Food; Future; Implant; In Situ Hybridization; Injection of therapeutic agent; Jaw; Label; Lateral; Lead; Light; Link; Location; Maps; Masseter Muscle; Mastication; Mediating; Mediator of activation protein; Motor; Motor Cortex; Motor Neurons; Movement; Movement Disorders; Mus; Muscle; Neurons; Neurotransmitters; Output; Play; Rabies; Rabies virus; Research; Role; Sensory; Signal Transduction; Slice; Subfamily lentivirinae; Symptoms; Synapses; Techniques; Temporomandibular Joint Disorders; Testing; Tetanus Toxin; Trigeminal System; Viral; Work; awake; base; feeding; food preparation; insight; jaw movement; motor control; nervous system disorder; neural circuit; neuromuscular; neuroregulation; novel; optogenetics; public health relevance; relating to nervous system

Determining Functions of a Brainstem Pre-motor Module In Masticatory Jaw Movement Project Summary/Abstract Mastication is a complex sensory-motor behavior necessary for the preparation of food for swallowing. The movement of the jaw plays a critical role in the breaking down of food. Abnormal jaw movements are manifested in several neurological disorders such as bruxism, temporomandibular joint disorders, and oromandibular dystonia. Thus, understanding the neural control of masticatory movements is essential for future development of effective and targeted treatments of these diseases. It is known that trigeminal motor neurons (MoVs) provide the main motor control of jaw muscles. However, the pre-motor circuits that provide direct inputs onto MoVs and thereby control their activity remain poorly understood. Furthermore, tonic stimulation applied to a sub-region of the jaw motor cortex deemed the cortical masticatory area (CMA) can activate rhythmic jaw movements. Yet the motor cortex is not known to form a direct connection with MoVs. The key groups of pre-motor neurons that relay cortical commands to MoVs have not been determined. In preliminary studies, a monosynaptic rabies virus based transsynaptic tracing technique was used to find that neurons located in the lateral paragigantocellular reticular nucleus (LPGi) are directly connected to MoVs innervating the main jaw closing muscle, the masseter, and that the number of LPGi premotor neurons that synapse onto the masseter MoVs dramatically increases with the transition from suckling to chewing behavior. These findings, together with previous studies, lead me to propose a central hypothesis: MoV pre-motor neurons in the LPGi form a critical neural module to relay cortical signals both directly onto jaw closing MoVs and onto other pre-motor neurons in the brainstem reticular network to enable rhythmic and tonic jaw movements. I will use optogenetic-assisted slice electrophysiology to determine functional connectivity between LPGi pre-motor neurons and other proposed neuronal groups. I will use optogenetic activation and inhibition to determine the role of LPGi pre-motor neurons in cortically-induced fictive rhythmic jaw movements in anesthetized mice. Finally, I will examine the consequences of silencing LPGi pre-motor neurons in natural mastication in awake behaving mice. These studies are expected to provide much needed novel insights into the precise neural circuitry controlling jaw movement and masticatory behavior.

咀嚼运动中脑干前运动模块的功能决定 项目总结/摘要 咀嚼是一种复杂的感觉-运动行为，是准备吞咽食物所必需的。 颌的运动在食物的分解中起着关键的作用。不正常的下颌运动是 表现为几种神经系统疾病，如磨牙症、颞下颌关节疾病， 口下颌肌张力障碍因此，了解咀嚼运动的神经控制对于 这些疾病的有效和有针对性的治疗方法的未来发展。 已知三叉神经运动神经元（MoV）提供颌肌肉的主要运动控制。 然而，为MoV提供直接输入从而控制其活动的前运动回路仍然存在， 不太了解。此外，对下颌运动皮层的一个子区域施加强直刺激， 皮层咀嚼区（CMA）可以激活有节奏的下颌运动。然而，运动皮层并不知道 与电影直接联系。传递皮层命令的关键前运动神经元群 MoV尚未确定。 在初步研究中，使用了基于单突触狂犬病病毒的跨突触追踪技术 发现位于外侧巨细胞旁网状核（LPGi）的神经元与 运动神经支配的主要颌骨关闭肌肉，咬肌，和数量的LPGi运动前 与咬肌MoV突触的神经元随着从哺乳到哺乳的过渡而显著增加。 咀嚼行为这些发现，加上以前的研究，让我提出一个中心假设： LPGi中的MoV前运动神经元形成关键的神经模块，以将皮质信号直接传递到 下颌闭合MoV和脑干网状网络中的其他前运动神经元上， 和紧张性下颌运动。我将使用光遗传学辅助切片电生理学来确定功能 LPG 1前运动神经元和其他提出的神经元组之间的连接。我会用光遗传学 激活和抑制，以确定LPGi前运动神经元在皮质诱导的虚构节律中的作用。 麻醉小鼠的下颌运动。最后，我将研究LPGi预电机静音的后果 神经元在清醒的小鼠自然咀嚼中的作用。这些研究有望提供急需的 对控制下颌运动和咀嚼行为的精确神经回路的新见解。