Descending Control of Orofacial Behavior

口面部行为的降序控制

• 批准号: 10413916
• 负责人: David Kleinfeld
• 金额: $ 54.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413916
• 关键词: Affinity Chromatography; Anatomy; Anterior; Atlases; Automobile Driving; Basal Ganglia; Behavior; Behavioral; Behavioral Assay; Brain Stem; Cell Nucleus; Cells; Complement; Consumption; Coupled; Data; Dissection; Exploratory Behavior; Future; Gene Expression; Genetic; Goals; Grain; Individual; Label; Lateral; Lead; Location; Measures; Messenger RNA; Methods; Modeling; Molecular Profiling; Motor; Motor Cortex; Motor Neurons; Movement; Mus; Muscle; Neurons; Pathway interactions; Periodicity; Play; Population; Research Project Grants; Reticular Formation; Reverse engineering; Rewards; Ribosomes; Role; Signal Transduction; Source; Substantia nigra structure; System; Techniques; Technology; Texture; Time; Tongue; Training; Translating; Vibrissae; Whole-Cell Recordings; base; deep sequencing; design; digital; high risk; hypoglossal nucleus; motor control; neural circuit; neuromechanism; neuronal circuitry; neurotransmission; next generation; optogenetics; orofacial; superior colliculus Corpora quadrigemina; theories; transcriptome

Project 3. Abstract Descending control of orofacial behavior (Kleinfeld lead; Mukamel, Svoboda, Wang) This Research Project will define the connectivity and neural mechanisms of descending control by motor cortex of orofacial behavior. Orofacial movements can be rhythmic and coordinated with each other. However, individual movements can also be specifically controlled to achieve behavioral goals, such as consuming a reward at a particular location and time. We will use a behavioral assay in which mice have to make a directional tongue movement at a particular time to receive a reward. This further serves as an example of set- point control. The brainstem level controls for licking are driven by the motor neurons in the hypoglossal nucleus whose activity in turn is modulated by premotor neurons in the intermediate nucleus of the reticular formation. Our studies will explore the anatomical connectivity, i.e. “Components” and signal flow, i.e., ”Wiring Diagrams” that converge on this region of the reticular formation. We will further refine the description of hypoglossal premotor subregions, nominally referred to here as “hIRt”, that are relevant to licking. Our preliminary data indicates that motor cortex can direct the timing of licking bouts and direction of licking, but not the timing of individual licks. We will trace these command signals from the motor cortex through the superior colliculus and into the hIRt. We will measure neural signals in another descending pathway from the basal ganglia that converges on the superior colliculus and the hIRt. We will measure how these descending inputs are synaptically coupled to defined neuron types in the hIRt. Together this project will provide a mechanistic account of how descending signals from multiple sources are integrated at the level of premotor neurons in the brainstem, complementing our studies on projections that control the set-point of whisking (Project 2). An additional focus will set the stage for the next generation dissection of the neural circuits in the brainstem. This requires molecular profiling of specific cell classes to provide transcriptomes that will facilitate future fine-grained analyses, including genetic labeling, manipulation, and transsynaptic tracing. Specific populations of premotor neurons will be isolated by transsynaptic labeling and mRNA will be isolated using Translating Ribosome Affinity Purification (TRAP), a technology that isolates mRNAs associated with translating ribosomes and is especially favorable in the densely myelinated brainstem. This is followed by deep sequencing and yields a new method, TRAP:Seq.

项目3。摘要 口面行为的下行控制（克莱菲尔德导联; Mukamel、Svoboda、Wang） 本研究计划将探讨运动控制下行的神经连结与神经机制 口面行为皮层口面运动可以是有节奏的，并且彼此协调。然而，在这方面， 还可以具体地控制个体运动以实现行为目标，例如消耗 在特定的时间和地点获得奖励。我们将使用一种行为分析，在这种分析中，小鼠必须做出一个 在特定的时间进行有方向的舌头运动以获得奖励。这也是一个例子， 点控制。脑干水平控制舔是由舌下神经的运动神经元驱动的 其活动又受网状核中间核中的运动前神经元调节的核 阵我们的研究将探讨解剖连接，即“组件”和信号流，即，“接线 在网状结构的这个区域汇聚的“图解”。我们将进一步完善对 舌下神经运动前亚区，在此名义上称为“hIRt”，其与舔相关。 我们的初步数据表明，运动皮层可以指导舔的时机和方向， 但不是每次舔的时间我们将追踪这些来自运动皮层的指令信号， 上级丘进入hIRt。我们将测量另一个下行通路中的神经信号， 会聚在上级丘和hIRt上的基底神经节。我们将测量这些下降的 输入突触耦合到hIRt中定义的神经元类型。该项目将为 一个机制的帐户如何下降的信号从多个来源整合在水平的前运动 脑干中的神经元，补充了我们对控制搅拌设定点的投射的研究 （项目2）。 一个额外的重点将为下一代解剖的神经回路的阶段， 脑干这需要对特定细胞类别进行分子分析，以提供转录组， 未来的细粒度分析，包括遗传标记，操纵和跨突触追踪。具体 运动前神经元群将通过跨突触标记分离，并且mRNA将使用 翻译核糖体亲和纯化（TRAP），一种分离与以下相关的mRNA的技术： 翻译核糖体，尤其是在有髓鞘的脑干中。其次是深 测序并产生一种新的方法，TRAP：Seq.