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（由申请人提供）：本项目的目标是提供有关的新信息 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，当我们 暴露于意想不到的刺激或潜在的威胁条件。几个精神和神经科的 这些疾病与运动张力和觉醒调节的损伤有关， 超敏反应、过度惊吓反应和焦虑增加。这项研究的重点是小脑， 大脑的一部分，以其协调运动和学习预测何时以及如何运动的作用而闻名。 运动，但也是重要的调节清醒状态唤醒水平。研究人员和临床医生目前缺乏 开发和针对患有以下疾病的患者的新治疗方法所需的具体信息 防御性唤起失调该项目的具体目标是提供解剖， 生理和功能信息的特定小脑细胞类型，调节运动的 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。到 为了实现这些目标，解剖电路分析将绘制特定神经元的差异突触连接性 小脑神经元，神经生理学分析将用于监测特定类型的小脑神经元的活动。 神经元在自发和感觉诱发的唤醒条件下， 分析将确定特定小脑细胞类型的操纵活动对在线和 对意外或潜在威胁刺激的唤醒反应的习得性调节。这些实验 将为开发药物或神经刺激疗法提供关键基础， 那些在调节如何应对意外威胁的能力方面受到损害的患者 刺激。