Descending engagement of brainstem neuronal circuits that govern orofacial motor behaviors

项目摘要 我打算研究啮齿类动物口面行为的神经元控制。成人口面行为 啮齿类动物包括摄食行为，如舔和咀嚼，以及探索行为，如 面部胡须的扫动、或"拂动"、嗅闻、以及定向的鼻子和头部运动。 婴儿从事吮吸行为，这涉及探索性的乳头寻找运动和摄食 吮吸动作哺乳动物的脑干包含了神经元网络， 行为，这些网络是由其他的，更多的嘴部部分的大脑，以确保 相关行为在适当的上下文中执行;也就是说，当适当的环境 存在内部感觉线索。我打算研究这些高级大脑区域是如何影响 适当的脑干网络模块，以实现动物的决定，执行适当的口面 运动行为。 在该项目的指导阶段，我将专注于识别神经元回路机制， 新生小鼠哺乳行为的基础，这一主题，尽管它对哺乳动物的生存很重要， 近年来被神经科学家们忽视了。为了识别在神经元细胞中活跃的神经元细胞类型， 在哺乳期，我一直在测量立即早期基因的共表达，沿着细胞类型特异性 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， 它们组成的神经回路。与此同时，我一直在开发新的病毒载体工具， 将现代分子示踪剂和致动器递送到出生后早期的小鼠大脑，以探测机制， 这些神经回路编码吮吸行为。在获奖期间，我将使用这些新工具（1） 映射识别出的吸吮活性神经元群体的输入/输出连接，以及（2）操纵 这些群体在体内的活性，以确定它们在产生和维持哺乳行为中的作用。在 独立阶段I将把我的重点扩展到更广泛的摄食和探索性口面 行为，目的是了解（3）前脑如何输入脑干orofacial前， 运动神经元可能门控这些行为的表达取决于环境和动机 上下文研究这种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 决策 在哈佛的凯瑟琳迪拉克博士的指导下进行的该项目的指导阶段 大学和博士塞缪尔普法夫在索尔克研究所，概述了一个全面的计划，收购一个 独特的技术和专业技能的结合，使我能够过渡到一个独立的 研究立场。

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.