Descending engagement of brainstem neuronal circuits that govern orofacial motor behaviors

项目概要 我建议研究啮齿动物口面部行为的神经元控制。成熟期的口面部行为 啮齿类动物包括诸如舔和咀嚼之类的摄取行为，以及诸如诸如此类的探索行为。 扫动面部胡须，或“拂动”、嗅嗅以及定向鼻子和头部运动。 婴儿会进行吸吮行为，其中包括探索性寻找乳头的动作和吞咽动作 吸吮动作。哺乳动物的脑干包含控制所有这些口面部的神经元网络 行为，并且这些网络由大脑的其他更靠近嘴部的部分指导，以确保 相关行为在适当的上下文中执行；也就是说，当环境和条件适当时 存在内部感官线索。我打算研究这些高阶大脑区域如何影响 适当的脑干网络模块来实现动物执行适当口面部手术的决定 电机法。 在项目的指导阶段，我将重点关注确定神经元回路机制 这是新生小鼠哺乳行为的基础，尽管这个话题对哺乳动物的生存很重要，但 近年来，神经科学家基本上忽视了这一点。识别在过程中活跃的神经元细胞类型 哺乳期，我一直在测量立即早期基因与细胞类型特异性的共表达 分子标记。然后我可以使用已识别的神经元细胞类型标记作为遗传入口点来追踪 它们组成的神经元回路。同时，我一直在开发新的病毒载体工具，以快速 将现代分子示踪剂和执行器传递到出生后早期小鼠大脑，以通过以下方式探究其机制 这些神经元回路编码哺乳行为。在奖励期间，我将使用这些新工具来 (1) 绘制已识别的哺乳活跃神经元群的输入/输出连接图，以及（2）操纵 这些种群在体内的活动，以确定它们在产生和维持哺乳行为中的作用。在 在独立阶段，我将把重点扩展到更广泛的摄取和探索性口面部 成年小鼠的行为，目的是了解（3）前脑如何输入脑干口面部前部 运动神经元可能会根据环境和动机来控制这些行为的表达 上下文。研究此类先天运动行为的脑干模块代表了研究的理想模型 大脑中连接的神经元网络如何控制简单的行为以及神经系统如何 决定。 该项目的指导阶段在哈佛大学 Catherine Dulac 博士的指导下进行 大学和索尔克研究所的塞缪尔·普法夫博士概述了收购 技术和专业技能的独特结合将使我能够过渡到独立 研究职位。

PROJECT SUMMARY I propose to investigate the neuronal control of orofacial behaviors in rodents. Orofacial behaviors in mature rodents include ingestive behaviors such as licking and chewing, as well as exploratory behaviors, such as sweeping movements of the facial whiskers, or “whisking”, sniffing, and directed nose and head movements. Infants engage in suckling behavior, which involves both exploratory nipple-seeking movements and ingestive sucking movements. The mammalian brainstem contains networks of neurons that control all of these orofacial behaviors, and these networks are directed by other, more rostral parts of the brain that ensure that the associated behaviors are executed in the appropriate context; that is, when the appropriate environmental and internal sensory cues are present. I intend to investigate how these higher-order brain areas influence the appropriate brainstem network modules to implement the animals’ decision to execute an appropriate orofacial motor act. In the mentored phase of the project, I will focus on identifying the neuronal circuit mechanisms that underlie suckling behavior in newborn mice, a topic which, despite its importance for mammalian survival, has been largely ignored by neuroscientists in recent years. To identify neuronal cell-types that are active during suckling, I have been measuring the co-expression of immediate-early-genes along with cell-type specific molecular markers. I can then use the identified neuronal cell-type markers as genetic entry-points to trace the neuronal circuits they comprise. At the same time, I have been developing new viral vector tools to rapidly deliver modern molecular tracers and actuators to the early postnatal mouse brain to probe the mechanisms by which these neuronal circuits code suckling behavior. During the award period, I will use these new tools to (1) map the input/output connectivity of identified suckling-active neuronal populations, and (2) manipulate the activity of these populations in-vivo to determine their roles in generating and maintaining suckling behavior. In the independent phase I will extend my focus to the broader repertoire of ingestive and exploratory orofacial behaviors in adult mice, with the goal of understanding (3) how forebrain inputs to brainstem orofacial pre- motoneurons may gate the expression of these behaviors depending on the environmental and motivational context. Investigating the brainstem modules for such innate motor acts represent an ideal model for studying how networks of connected neurons in the brain control simple behaviors and how nervous systems make decisions. The mentored phase of the project, conducted under the direction of Dr. Catherine Dulac at Harvard University and Dr. Samuel Pfaff at the Salk Institute, outlines a comprehensive plan for the acquisition of a unique combination of technical and professional skills that will enable my transition to an independent research position.