Vestibular control of axial motor circuitry

轴向运动电路的前庭控制

• 批准号: 9198220
• 负责人: Martha W Bagnall
• 金额: $ 24.12万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-08 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9198220
• 关键词: Animals; Axon; Behavior; Behavior Control; Behavioral; Brain Stem; Calcium; Calcium Signaling; Cells; Classification; Contralateral; Data; Diabetes Mellitus; Dorsal; Dyes; Ear; Elderly; Electrophysiology (science); Electroporation; Elements; Environment; Equilibrium; Esthesia; Fishes; Force of Gravity; Future; Goals; Gravitation; Health Hazards; Human; Image; Impairment; Interneurons; Ipsilateral; Label; Labyrinth; Left; Limb structure; Locomotion; Mammals; Measures; Methods; Morphology; Motion; Motor; Motor Neurons; Motor output; Movement; Muscle; Musculoskeletal Equilibrium; Neurons; Neuropathy; Organism; Output; Pathway interactions; Pattern; Phase; Posture; Recruitment Activity; Research; Role; Self-control as a personality trait; Sensory; Side; Signal Transduction; Specificity; Spinal; Spinal Cord; Swimming; Synapses; System; Testing; Therapeutic Intervention; Torque; Training; Transgenic Organisms; Translating; Vertebral column; Vertebrates; Vertigo; Zebrafish; awake; cell type; experimental study; falls; fictional works; improved; in vivo; limb movement; motor control; mutant; neural circuit; novel; otoconia; sensor; sensory input; vestibulo-ocular reflex

Project Summary Good control of posture and orientation is vital for animals as they make movements or navigate the environment. Vertebrates rely on the vestibulospinal system to translate gravity sensations from the inner ear into appropriate compensatory trunk (axial) and limb movements to stabilize and orient themselves. Although this system exists in all vertebrates and is crucial for survival, research on it has languished due to the technical difficulties in recording from vestibular and spinal neurons, especially during animal motion. My long-term goal is to define the means by which vestibular and cerebellar pathways influence spinal circuit activity patterns to fine-tune behavioral outputs. The objective of this proposal is to determine how vestibular signals are translated into appropriate compensatory postural adjustments by defining the synaptic circuit by which vestibular neurons govern the activity of spinal motor neurons and interneurons. To surmount the technical difficulties that have limited prior efforts, I propose to use the larval zebrafish. Zebrafish are an excellent system for this line of research because of the accessibility of their brainstem and spinal column, and the strong homologies between zebrafish and mammalian spinal circuits. Thus, circuit mapping between the brainstem and spinal cord can be performed with much greater ease than in mammalian systems, and the results are likely to be applicable across vertebrates. Microcircuit activity can then be translated into behavioral output due to the relative simplicity of the zebrafish body plan, yielding a complete picture of this vital sensorimotor transformation. In Aim 1, a combination of calcium signaling and electrophysiology in vivo will be used to examine differential recruitment of dorsal and ventral musculature while the animal attempts to right itself from side-lying to upright. The requirement for vestibular signals will be tested in mutant animals missing their otoliths (gravity sensors). These experiments will identify how motor pools are activated by vestibular signals to drive self-righting. In Aim 2, vestibular neurons will be stimulated during in vivo recordings from identified spinal motor neurons to test how vestibulospinal drive is distributed to the appropriate pools of motor neurons for self-righting. Finally, Aim 3 will extend this research to spinal interneurons, to identify how descending inputs regulate interneuronal circuits for highly specific modulation of movement. Impairments in vestibulospinal signaling can cause vertigo and falls, a major health hazard in the elderly. Thus, a complete sensory-to-motor analysis of vestibulospinal signaling will advance our understanding of descending control of behavior and potentially identify strategies for improving human postural control.

项目摘要 良好的姿势和定向的控制对于动物进行动作或导航至关重要 环境。脊椎动物依靠前庭脊髓系统从内耳转化重力感觉 进入适当的补偿躯干（轴向）和肢体运动，以稳定和定向。虽然 该系统存在于所有脊椎动物中，对于生存至关重要，由于技术的研究而对其进行研究。 从前庭和脊柱神经元记录的困难，尤其是在动物运动过程中。我的长期 目标是定义前庭和小脑途径影响脊柱电路活动的手段 微调行为输出的模式。该建议的目的是确定前庭信号 通过定义突触电路，将其转化为适当的补偿性姿势调整 前庭神经元控制脊柱运动神经元和中间神经元的活性。克服技术 我建议使用幼虫斑马鱼的困难。斑马鱼很棒 由于其脑干和脊柱的可及性，并且强大 斑马鱼和哺乳动物脊柱回路之间的同源性。因此，脑干之间的电路映射 脊髓可以比在哺乳动物系统中更容易进行，结果是 可能适用于脊椎动物。然后可以将微电路活动转化为行为输出 由于斑马鱼身体计划的相对简单性，产生了这种重要感觉运动的完整图片 转型。在AIM 1中，体内钙信号传导和电生理学的组合将用于 在动物试图正确的同时，检查背侧和腹肌肉的差异招募 从侧面到直立。前庭信号的需求将在缺失的突变动物中进行测试 它们的耳石（重力传感器）。这些实验将确定如何通过前庭激活电动池 驱动自瞄准的信号。在AIM 2中，将在体内记录中刺激前庭神经元 确定的脊柱运动神经元，以测试前庭脊髓驱动如何分布到适当的池 运动神经元用于自晶。最后，AIM 3将将这项研究扩展到脊柱中间神经元，以确定如何 下降的输入调节神经元电路，以高度特异性的运动调节。障碍 前庭脊髓信号传导可能会导致眩晕和瀑布，这是老年人的主要健康危害。因此，一个完整 前庭脊髓信号传导的感觉到运动分析将提高我们对降落控制的理解 行为并有可能确定改善人类姿势控制的策略。