Transformation of the stress response into motor behavior by the external globus pallidus

外部苍白球将应激反应转化为运动行为

• 批准号: 9897542
• 负责人: NICHOLAS J JUSTICE
• 金额: $ 46.68万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-05 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897542
• 关键词: Amygdaloid structure; Anatomy; Animals; Anxiety; Area; Automobile Driving; Basal Ganglia; Basal Ganglia Diseases; Behavioral; Behavioral Assay; Biological Assay; Brain; Cell Nucleus; Cells; Corpus striatum structure; Corticotropin-Releasing Hormone; Corticotropin-Releasing Hormone Receptors; Direct immunofluorescence; Disease; Electrophysiology (science); Environment; Fiber Optics; Freezing; Globus Pallidus; Huntington Disease; Hypothalamic structure; Impairment; Implant; Knowledge; Label; Light; Maps; Mental Depression; Motor; Movement; Mus; Neurodegenerative Disorders; Neurons; Neuropeptides; Output; Parkinson Disease; Pathway interactions; Pattern; Physiology; Property; Publications; Rabies; Regulation; Signal Transduction; Specificity; Stress; Structure of subthalamic nucleus; Structure of terminal stria nuclei of preoptic region; Symptoms; Synapses; Testing; Thalamic structure; Viral; Work; anxiety states; anxiety-related behavior; base; biological adaptation to stress; designer receptors exclusively activated by designer drugs; experimental study; externalizing behavior; in vivo; insight; motor behavior; neural circuit; neuroregulation; novel; optogenetics; paraventricular nucleus; patch clamp; postsynaptic; presynaptic; receptor; release factor; response; restraint stress; stress state

Project Summary By controlling the activity of cortex, the basal ganglia is critical to the organization of motor commands. However, how information about the context in which a movement is executed is communicated to the basal ganglia is poorly understood. In particular, connections between stress activated nuclei in the hypothalamus, amygdala, and bed nucleus of the stria terminalis (BST) that respond to threats in the environment, and the basal ganglia are poorly characterized. This proposal uses the expression and localization of the stress neuropeptide, Corticotropin Releasing Factor (CRF), and its primary receptor, CRFR1 to uncover how stress signals reach the basal ganglia. Within the basal ganglia, CRFR1 is highly expressed by a subset of neurons in the external Globus Pallidus (GPe). In preliminary experiments, we traced the inputs to CRFR1 neurons in the GPe and found novel connections from CRF neurons in stress responsive nuclei. We hypothesize that previously unmapped circuits from these nuclei coordinate stress-induced movement via the GPe. In this proposal, we will test this hypothesis using three parallel strategies. First, we aim to map the connectivity of CRF-rich, stress responsive nuclei with the GPe using monosynaptic rabies viral tracing, direct immunofluorescence, and optogenetics assisted circuit mapping. Then, we will test the functional impact of CRF on the properties of synaptic connections between these nuclei. Finally, we will activate or inhibit particular pathways and assay resulting anxiety-related behavior to determine how the GPe acts to bias movement in stress-relevant contexts. The experiments proposed will probe the anatomy, physiology, and function of the robust, but poorly described connection between limbic circuits that respond to stress and basal ganglia circuits that pattern movement.

项目摘要 通过控制皮层的活动，基底神经节对运动命令的组织至关重要。然而，在这方面， 关于执行运动的背景的信息是如何传达到基底神经节的， 不太了解。特别是，压力激活下丘脑，杏仁核， 和床核的终纹（BST）的反应，在环境中的威胁，和基底神经节是 特征不佳。这项建议利用表达和定位的应激神经肽，促肾上腺皮质激素 释放因子（CRF）及其主要受体CRFR1，以揭示压力信号如何到达基底神经节。 在基底神经节内，CRFR1由外部苍白球（GPe）中的神经元子集高度表达。 在初步实验中，我们追踪了GPe中CRFR1神经元的输入，并发现了新的连接 应激反应核中的CRF神经元。我们假设，以前未映射的电路，从这些 核通过GPe协调应力诱导的运动。在本提案中，我们将使用三个 平行策略。首先，我们的目标是使用以下方法绘制CRF丰富的应激反应核团与GPe的连接图： 单突触狂犬病病毒追踪、直接免疫荧光和光遗传学辅助电路作图。然后， 我们将测试CRF对这些核团之间突触连接特性的功能影响。最后， 我们将激活或抑制特定的途径，并分析由此产生的焦虑相关行为，以确定如何 GPe在与压力相关的环境中作用于偏置运动。所提出的实验将探索解剖学， 生理学和功能的强大，但描述不佳的边缘电路之间的连接，响应 压力和基底神经节回路决定运动模式。