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

基本信息

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
项目类别：
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

项目摘要

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.

确定脑干前运动模块在咀嚼颌运动中的功能项目概要/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。下巴的运动在食物的分解中起着至关重要的作用。下颌运动异常是表现为磨牙症、颞下颌关节紊乱等多种神经系统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未来开发这些疾病的有效和有针对性的治疗方法。众所周知，三叉神经运动神经元（MoV）提供下颌肌肉的主要运动控制。然而，向 MoV 提供直接输入并从而控制其活动的前电机电路仍然存在不太了解。此外，施加于下颌运动皮层子区域的强直刺激被认为是皮质咀嚼区（CMA）可以激活有节奏的下颌运动。然而运动皮层尚不知道与 MoV 形成直接连接。传递皮质命令的关键前运动神经元组 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副巨细胞网状核（LPGi）的神经元直接相连神经支配主要下颌闭合肌、咬肌的 MoV，以及 LPGi 前运动的数量随着从哺乳期到哺乳期的转变，突触到咬肌 MoV 的神经元急剧增加。咀嚼行为。这些发现与之前的研究一起使我提出了一个中心假设： LPGi 中的 MoV 前运动神经元形成一个关键的神经模块，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，以实现有节奏的和强直下颌运动。我将使用光遗传学辅助切片电生理学来确定功能 LPGi 前运动神经元和其他提出的神经元群之间的连接。我将使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，我将研究使 LPGi 电机前静音的后果清醒行为小鼠自然咀嚼的神经元。这些研究预计将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颖见解。