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）：当动物进行运动或在环境中导航时，良好的姿势和方向控制对动物至关重要。脊椎动物依靠前庭脊髓系统将内耳的重力感觉转化为适当的补偿性躯干（轴向）和肢体运动，以稳定和定位自己。虽然这个系统存在于所有脊椎动物中，并且对生存至关重要，但由于前庭和脊髓神经元记录的技术困难，特别是在动物运动期间，对它的研究一直停滞不前。我的长期目标是确定前庭和小脑通路影响脊髓回路活动模式以微调行为输出的方法。这个建议的目的是确定如何前庭信号被翻译成适当的补偿姿势调整，通过定义的突触回路，前庭神经元支配脊髓运动神经元和中间神经元的活动。为了克服限制先前努力的技术困难，我建议使用斑马鱼幼虫。由于其脑干和脊柱的可接近性，以及斑马鱼和哺乳动物脊髓回路之间的高度同源性，斑马鱼是这一研究领域的优秀系统。因此，脑干和脊髓之间的电路映射可以比在哺乳动物系统中更容易地进行，并且结果可能适用于脊椎动物。由于斑马鱼身体结构相对简单，微电路活动可以转化为行为输出，从而产生这种重要的感觉运动转变的完整画面。在目标1中，将使用体内钙信号和电生理学的结合来检查动物试图从侧卧到直立时背侧和腹侧肌肉组织的差异募集。对前庭信号的要求将是 在失去耳石（重力感应器）的突变动物身上进行测试。这些实验将确定运动池是如何被前庭信号激活以驱动自我扶正的。在目标2中，将在来自鉴定的脊髓运动神经元的体内记录期间刺激前庭神经元，以测试前庭脊髓驱动如何分布到适当的运动神经元池以进行自我扶正。最后，Aim 3将把这项研究扩展到脊髓中间神经元，以确定下行输入如何调节高度特异性的运动调制的中间神经元回路。前庭脊髓信号的损伤会导致眩晕和福尔斯，这是老年人的主要健康危害。因此，一个完整的前庭脊髓信号的感觉到运动的分析将推进我们的理解下行控制的行为和潜在的识别策略，以改善人类的姿势控制。