Vestibular control of axial motor circuitry

轴向运动电路的前庭控制

基本信息

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
项目类别：
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

项目摘要

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.

项目概要当动物进行运动或导航时，良好的姿势和方向控制对于它们至关重要环境。脊椎动物依靠前庭脊髓系统来传递内耳的重力感觉进行适当的代偿性躯干（轴向）和肢体运动以稳定和定向自身。虽然该系统存在于所有脊椎动物中，对于生存至关重要，但由于技术原因，对其的研究已经陷入停滞。记录前庭和脊髓神经元的困难，特别是在动物运动期间。我的长期目标是定义前庭和小脑通路影响脊髓回路活动的方式调整行为输出的模式。该提案的目的是确定前庭信号如何通过定义突触回路将其转化为适当的补偿性姿势调整前庭神经元控制脊髓运动神经元和中间神经元的活动。为克服技术难题由于之前的努力有限，我建议使用斑马鱼幼体。斑马鱼是一种优秀的由于脑干和脊柱的可及性，以及强大的斑马鱼和哺乳动物脊髓回路之间的同源性。因此，脑干之间的电路映射与哺乳动物系统相比，脊髓的执行要容易得多，结果是可能适用于脊椎动物。然后微电路活动可以转化为行为输出由于斑马鱼的身体结构相对简单，因此可以完整了解这种重要的感觉运动转变。在目标 1 中，将结合体内钙信号传导和电生理学当动物试图恢复原状时，检查背侧和腹侧肌肉组织的募集差异从侧卧到直立。对前庭信号的需求将在缺失的突变动物中进行测试他们的耳石（重力传感器）。这些实验将确定前庭神经如何激活运动池驱动自动扶正的信号。在目标 2 中，前庭神经元将在体内记录过程中受到刺激识别脊髓运动神经元来测试前庭脊髓驱动如何分配到适当的池运动神经元用于自我纠正。最后，目标 3 将把这项研究扩展到脊髓中间神经元，以确定如何下降的输入调节神经元间回路，以实现高度特异性的运动调节。减值前庭脊髓信号传导可导致眩晕和跌倒，这是老年人的主要健康危害。这样，一个完整的前庭脊髓信号的感觉到运动分析将增进我们对下行控制的理解行为并可能确定改善人类姿势控制的策略。