Vestibular control of axial motor circuitry

项目摘要 良好的姿势和方向控制对于动物在移动或导航时是至关重要的 环境。脊椎动物依靠前庭脊髓系统来转换来自内耳的重力感觉 进入适当的代偿性躯干(轴向)和肢体运动，以稳定和定位自己。虽然 这种系统存在于所有脊椎动物中，对生存至关重要，由于技术上的原因，对它的研究一直处于停滞状态 前庭和脊髓神经元的记录困难，特别是在动物运动时。我的长期生活 目的是确定前庭和小脑通路影响脊髓环路活动的方式。 微调行为输出的模式。这项建议的目标是确定前庭信号是如何 通过定义突触回路，转化为适当的补偿性姿势调整 前庭神经元支配脊髓运动神经元和中间神经元的活动。要超越技术上的 这些困难限制了以前的努力，我建议使用斑马鱼幼体。斑马鱼是一种极好的 对于这一行的研究系统，因为他们的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 脊髓可以比在哺乳动物系统中更容易地进行手术，结果是 可能适用于所有脊椎动物。然后，微电路活动可以转化为行为输出 由于斑马鱼的身体规划相对简单，因此可以完整地了解这种重要的感觉运动 转型。在目标1中，钙信号和体内电生理学的结合将被用于 动物尝试站立时，检查背侧和腹侧肌肉系统的不同募集 从侧卧到直立。对前庭信号的要求将在缺失的突变动物身上进行测试 他们的耳石(重力传感器)。这些实验将确定前庭是如何激活运动池的 驱动自我恢复的信号。在目标2中，前庭神经元将在活体记录期间被刺激 确定脊髓运动神经元，以测试前庭脊髓驱动如何分配到适当的 自立的运动神经元。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 下行输入调节神经元间回路，以实现高度特异的运动调节。减值 前庭脊髓信号可导致眩晕和跌倒，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-运动分析将促进我们对前庭脊髓信号下行控制的理解 并潜在地确定改善人体姿势控制的策略。

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.