Descending engagement of brainstem neuronal circuits that govern orofacial motor behaviors

控制口面部运动行为的脑干神经元回路的下降参与

基本信息

批准号：
10804889
负责人：
Jeffrey Daniel Moore
金额：
$ 24.89万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10804889
关键词：
Ablation Adult Amygdaloid structure Animals Area Award Axon Behavior Behavior Control Behavioral Brain Brain Stem Brain region Code Complex Cre driver Cues Data Decision Making Deglutition Elements Engineering Ensure Environment Exhibits Exploratory Behavior Face Feeding behaviors Genetic Genetic Techniques Goals Head Movements Hypothalamic structure Immediate-Early Genes Infant Investigation Knowledge Label Legal patent Life Link Logic Mammals Maps Mastication Measures Mediating Mentors Modernization Molecular Monitor Mothers Motivation Motor Motor Neurons Movement Mus Nervous System Neurobiology Neurodegenerative Disorders Neurons Neuropeptide Gene Neuropeptide Receptor Neurosciences Newborn Infant Nipples Nose Output Parkinson Disease Pathology Pathway interactions Pattern Phase Physiological Play Population Positioning Attribute Prosencephalon Proteins Reporting Research Research Personnel Rodent Role Sensory Shapes Structure Study models Surveys Symptoms Synapses System Techniques Testing Time Tracer Training Universities Vascular Dementia Vibrissae Viral Viral Vector Work behavior test cell type experimental study feeding in vivo mature animal mind control molecular marker motor behavior neuronal circuitry novel optogenetics oral reflex orofacial postnatal postnatal development preference presynaptic skills sucking suckling tool vector

项目摘要

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.

项目概要我建议研究成熟啮齿类动物口面部行为的神经控制。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，以确保相关行为是在适当的环境下执行的；我打算研究这些高级大脑区域如何影响内部感觉线索。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回路机制这是新生小鼠哺乳行为的基础，尽管这个话题对于哺乳动物的生存很重要，但近年来，神经科学家在很大程度上忽视了识别活动期间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然后我可以使用识别出的神经细胞类型标记作为遗传入口点来追踪与此同时，我一直在开发新的病毒载体工具以快速实现。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回路编码哺乳行为。在颁奖期间，我将使用这些新工具来 (1) 绘制已识别的哺乳活跃神经群体的输入/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研究这种先天运动行为的脑干模块是一个理想的研究模型。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。