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

• 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
• 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

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.

项目总结 我建议研究啮齿类动物口面部行为的神经元控制。成熟期的口面部行为 啮齿动物包括摄食行为，如舔和咀嚼，以及探索行为，如 面部胡须的全面运动，或“搅拌”，嗅探，并指示鼻子和头部的运动。 婴儿会进行哺乳行为，包括探索性的乳头运动和进食。 令人恶心的动作。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，而这些网络由大脑的其他更多的嘴部引导，确保 关联的行为在适当的上下文中执行；即，当适当的环境和 存在内在的感官暗示。我打算调查这些高阶大脑区域是如何影响 适当的脑干网络模块，以实现动物执行适当的口面部手术的决定 机动法。 在该项目的指导阶段，我将专注于确定神经回路机制 这是新生小鼠哺乳行为的基础，这个话题尽管对哺乳动物的生存很重要，但已经 近年来在很大程度上被神经学家忽视了。识别活跃的神经细胞类型 Suckling，我一直在测量即刻-早期-基因的共表达以及细胞类型特异性 分子标记。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 它们构成了神经元回路。与此同时，我一直在开发新的病毒载体工具，以迅速 将现代分子示踪剂和致动器送入出生后早期的小鼠大脑，通过以下方式探索其机制 这些神经回路编码哺乳行为。在获奖期间，我将使用这些新工具来(1) 映射已识别的哺乳活动神经元群体的输入/输出连接性，以及(2)操纵 这些种群在活体内的活动，以确定它们在产生和维持哺乳行为中的作用。在……里面 独立的第一阶段将把我的注意力扩展到更广泛的摄食和探索口腔面部的剧目 成年小鼠的行为，目的是了解(3)前脑如何传入脑干-口面部前- 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 背景。研究这种先天运动行为的脑干模块是研究的理想模型 大脑中相互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，在哈佛大学凯瑟琳·杜拉克博士的指导下进行 大学和索尔克研究所的Samuel Pfaff博士概述了一项全面的收购计划 独特的技术和专业技能组合，将使我能够过渡到独立的 研究职位。