Descending Control of Orofacial Behavior

项目3.摘要 口腔行为的下降控制(Kleinfeld Lead；Mukamel，Svoboda，Wang) 这项研究项目将确定电机下行控制的连通性和神经机制 口面部行为的皮质。口腔面部的运动可以是有节奏的，并且相互协调。然而， 还可以专门控制个人的运动，以实现行为目标，例如消耗 在特定的地点和时间奖励。我们将使用一种行为测试，在该测试中，小鼠必须做出 舌头在特定时间进行定向运动以获得奖励。这进一步作为SET的一个例子-- 点控制。舔食的脑干水平控制是由舌下运动神经元驱动的 其活动依次受网状结构中间核中的运动前神经元调节的核 队形。我们的研究将探索解剖上的连通性，即“组件”和信号流，即“布线” 图“汇聚在网状结构的这一区域。我们将进一步细化对 舌下运动前亚区，在这里名义上被称为“Hirt”，与舔相关。 我们的初步数据表明，运动皮质可以指导舔咬的时间和方向， 但不是个别舔的时间。我们将追踪这些来自运动皮质的指令信号 上丘进入发情区。我们将测量另一条下行通路中的神经信号 汇聚于上丘和丘脑的基底节。我们将测量这些下降的 在Hirt中，输入与定义的神经元类型是突触耦合的。该项目将共同提供一个 对来自多个信号源的下行信号如何在前置电机水平上进行整合的机械描述 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)。 另一个关注点将为下一代对 脑干。这需要特定细胞类别的分子图谱来提供转录本，这将有助于 未来的细粒度分析，包括基因标记、操纵和跨突触追踪。特定的 将通过跨突触标记分离运动前神经元群体，并使用 翻译核糖体亲和纯化(TRAP)，一种分离与 翻译核糖体，尤其适用于髓鞘密集的脑干。紧随其后的是深度 测序，并产生了一种新的方法，TRAP：SEQ。

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.