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.

项目摘要 我建议研究啮齿动物中口面部行为的神经元控制。成熟的口面行为 啮齿动物包括摄取行为，例如舔和咀嚼，以及探索行为，例如 面晶须的动作，“搅动”，嗅探和鼻子和头部动作。 婴儿从事哺乳行为，既涉及探索性乳头的动作又涉及摄取 吮吸动作。哺乳动物脑干包含控制所有这些口面的神经元网络 行为和这些网络由大脑的其他更宽容的部分指导，以确保 相关的行为在适当的上下文中执行；也就是说，当适当的环境和 存在内部感觉提示。我打算调查这些高阶大脑区域如何影响 适当的脑干网络模块，以实施动物执行适当的口面的决定 运动法。 在项目的修订阶段，我将重点介绍确定神经元电路机制 新生老鼠的哺乳行为是基础，这个话题是其对哺乳动物生存的重要性的主题 近年来，神经科学家在很大程度上被忽略了。识别在 哺乳，我一直在测量立即生产的共表达以及细胞类型的特异性 分子标记。然后，我可以将确定的神经元细胞类型标记作为遗传入口点来追踪 他们完成的神经元电路。同时，我一直在开发新的病毒矢量工具来快速 将现代分子示踪剂和执行器传递到早期的产后小鼠大脑，以探测机制 这些神经元电路代码哺乳行为。在奖励期间，我将使用这些新工具来（1） 绘制已确定的哺乳活动神经元种群的输入/输出连接，（2）操纵 这些人群的活动在体内确定它们在产生和维持哺乳行为中的作用。在 独立阶段一世将把重点扩展到更广泛的摄入和探索性口面上的曲目 成年小鼠的行为，目的是理解（3）前脑对脑干口面上的投入如何 运动神经元可能会根据环境和激励性而对这些行为的表达 语境。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 大脑中连接神经元的网络如何控制简单行为以及神经系统如何使 决定。 该项目的修改阶段，在哈佛大学的凯瑟琳·杜拉克（Catherine Dulac）博士的指导下进行 Salk Institute的大学和Samuel Pfaff博士概述了收购的全面计划 技术和专业技能的独特组合，将使我过渡到独立 研究职位。