Cerebellar Fastigial Motor and Non-motor Circuits

小脑小脑顶运动和非运动电路

• 批准号: 10713385
• 负责人: SASCHA DU LAC
• 金额: $ 52.13万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713385
• 关键词: Affective; Anatomy; Animal Model; Anxiety; Arousal; Basal Ganglia; Behavior; Behavioral; Brain; Brain Stem; Cell Nucleus; Cerebellar Nuclei; Cerebellar vermis structure; Cerebellum; Cerebral cortex; Clinical; Cognitive; Collection; Coupled; Diagnosis; Electrocorticogram; Electrophysiology (science); Event; Exposure to; Eye; Fire - disasters; Foundations; Functional disorder; Goals; Head; Human; Hypersensitivity; Impairment; Laboratories; Learning; Limbic System; Maps; Medial; Mediating; Mental disorders; Methods; Monitor; Motor; Movement; Mus; Neck; Neurons; Nucleus fastigii; Output; Patients; Physiological; Physiology; Play; Pontine structure; Positioning Attribute; Posture; Regulation; Reporter; Research; Research Personnel; Research Project Grants; Rewards; Role; Sensory; Silicones; Site; Startle Reaction; Stimulus; Synapses; Techniques; Therapeutic; Vestibular nucleus structure; Viral; awake; cell type; cholinergic; experience; experimental study; genetic manipulation; imaging study; motor control; motor symptom; multidisciplinary; nervous system disorder; neural circuit; neurophysiology; neuropsychiatric disorder; new therapeutic target; non-motor symptom; noradrenergic; oculomotor; optogenetics; pharmacologic; postsynaptic; presynaptic; response; sensory stimulus; tool

Project Summary DESCRIPTION (provided by applicant): The goal of this project is to provide new information about the specific brain circuits which enable us to regulate our posture, movements, and arousal levels when we are exposed to unexpected stimuli or potentially threatening conditions. Several psychiatric and neurological disorders are associated with impairments in motor tone and arousal regulation which manifest as sensory hypersensitivity, excessive startle reactivity, and increased anxiety. This research focuses on the cerebellum, a part of the brain known best for its role in coordinating movements and learning to anticipate when and how to move, but is also important for regulating wake-state arousal levels. Researchers and clinicians currently lack specific information needed to develop and target new therapeutic treatments to patients who suffer from dysregulation of defensive arousal. The specific objectives of this project are to provide anatomical, physiological, and functional information about specific cerebellar cell types which regulate movements of the trunk, head and eyes and levels of arousal via their synaptic connections with brainstem control centers. To achieve these objectives, anatomical circuit analyses will map differential synaptic connectivity of specific cerebellar neurons, neurophysiological analyses will be used to monitor activity in specific types of cerebellar neurons under conditions of spontaneous and sensory- evoked arousal, and behavioral and physiological analyses will determine the impact of manipulating activity of specific cerebellar cell types on the online and learned regulation of arousal responses to unexpected or potentially threatening stimuli. These experiments will provide a critical foundation for developing pharmacological or neurostimulation therapies for treating patients who suffer from impairments in the abiilty to regulate how they respond to unexpected threatening stimuli.

项目摘要 描述(由申请者提供)：本项目的目标是提供有关 特定的大脑回路，使我们能够调节我们的姿势、动作和唤醒水平 暴露在意想不到的刺激或潜在的威胁条件下。几个精神科和神经科 精神障碍与运动音调和唤醒调节功能障碍有关，表现为感觉障碍。 过敏症，过度惊吓反应，焦虑增加。这项研究的重点是小脑，一种 大脑的一部分，最为人所知的是其协调运动的作用，并学习预测何时以及如何 移动，但对于调节觉醒状态的唤醒水平也很重要。研究人员和临床医生目前缺乏 开发新的治疗方法并将其作为治疗对象需要的具体信息 防御性唤醒的失调。这个项目的具体目标是提供解剖的， 有关特定小脑细胞类型的生理和功能信息，这些细胞类型调节 躯干、头部和眼睛，以及通过它们与脑干控制中心的突触连接的唤醒水平。至 为了实现这些目标，解剖电路分析将映射特定的不同突触连接 小脑神经元，神经生理学分析将被用来监测特定类型的小脑的活动 自发觉醒和感觉唤醒条件下的神经元，以及行为和生理状态 分析将确定特定小脑细胞类型的操纵活动对在线和 学会了对意外或潜在威胁刺激的唤醒反应的调节。这些实验 将为开发治疗药物或神经刺激疗法提供关键基础 患者在调节他们如何应对意外威胁的能力方面存在障碍 刺激物。