Vestibular control of axial motor circuitry

轴向运动电路的前庭控制

• 批准号: 8523831
• 负责人: Martha W Bagnall
• 金额: $ 9.23万
• 依托单位: NORTHWESTERN 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 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8523831
• 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; Environment; Equilibrium; Esthesia; Fishes; Force of Gravity; Future; Goals; Health Hazards; Human; Image; Impairment; Indium; Interneurons; Ipsilateral; Label; Labyrinth; Left; Limb structure; Locomotion; Mammals; Maps; Measures; Methods; 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; base; cell type; falls; improved; in vivo; limb movement; motor control; mutant; neural circuit; novel; otoconia; research study; sensor; vestibulo-ocular reflex

DESCRIPTION (provided by applicant): 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 du 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 n 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 relativ 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.

描述（由申请人提供）：良好的姿势和定向的控制对于动物进行运动或导航环境至关重要。脊椎动物依靠前庭脊髓系统将重力感觉从内耳转化为适当的补偿躯干（轴向）和肢体运动以稳定和定向。尽管该系统存在于所有脊椎动物中，并且对于生存至关重要，但对其进行的研究对录制的技术困难却使前庭和脊柱神经元（尤其是在动物运动过程中）陷入困境。我的长期目标是定义前庭和小脑途径影响脊柱电路活性模式以微调行为输出的手段。该提案的目的是通过定义前庭神经元控制脊柱运动神经元和中间神经元活动的突触回路，确定前庭信号如何转化为适当的补偿性姿势调节。为了克服先前努力的技术困难，我建议使用幼虫斑马鱼。斑马鱼是该研究线的n个绝佳系统，因为它们的脑干和脊柱的可及性以及斑马鱼和哺乳动物脊柱电路之间的强大同源性。因此，与哺乳动物系统相比，可以轻松地进行脑干和脊髓之间的电路映射，结果可能适用于脊椎动物。然后，由于斑马鱼身体计划的相对性简单性，微电路活性可以转化为行为输出，从而获得了这种重要的感觉运动转化的完整图片。在AIM 1中，体内钙信号传导和电生理学的组合将用于检查背侧和腹肌肉的差异募集，而动物试图从侧唇到直立。前庭信号的要求是 在缺少耳石（重力传感器）的突变动物中测试。这些实验将确定如何通过前庭信号激活电动机池以驱动自晶。在AIM 2中，将在识别的脊柱运动神经元的体内记录中刺激前庭神经元，以测试前庭脊髓驱动如何分布到适当的运动神经元库中以进行自我impligning。最后，AIM 3将将这项研究扩展到脊柱中间神经元，以确定下降的输入如何调节内神经元电路以高度特定的运动调节。前庭脊髓信号的障碍会导致眩晕和跌倒，这是老年人的主要健康危害。因此，对前庭脊髓信号传导的完整感觉到运动分析将提高我们对行为控制的下降的理解，并有可能确定改善人类姿势控制的策略。