Central control of rhythmic movement in a vertebrate

描述(申请人提供)：大多数脊椎动物的行为依赖于大脑和/或脊髓中许多神经元的协调活动。虽然已经研究了脊髓回路单次重复的组织和功能，但分布在节段上的中间神经元群体如何产生功能行为尚不清楚。这项研究的目的是研究脊髓中间神经元的纵向分布以及这些中间神经元群体在行为中的作用。这项工作利用斑马鱼幼虫模型系统中神经元成像的新技术，包括细胞群体活动成像和细胞特异性消融技术，来验证神经元间组织和功能的假说。目的1观察脊髓中间神经元的纵向分布，验证细胞内存在旋转尾部梯度的假设和运动回路中下行中间神经元的数量大小。目的2确定下行中间神经元在行为中的作用。细胞特异性损伤被用来移除一组中间神经元，并在这些消融前后对行为进行评估。目的2验证以下假设：去除下行兴奋性中间神经元将降低弯曲幅度、角速度和角加速度，并且对于有节奏的运动，会扰乱轴波的传播模式。这是第一次测试脊椎动物中脊髓中间神经元的作用。目标3连接目标1和目标2，通过对消融细胞下游的一组神经元的细胞活动进行成像，解决中间神经元如何影响其行为角色。我们假设，消融兴奋性惊厥中间神经元会降低消融区中间神经元和运动神经元的活动，与消融细胞的数量成比例，但不会改变尾部的活动。我们假设，消融兴奋性游泳中间神经元将降低消融区域及其尾部的中间神经元活动。这项建议的目的是通过测试细胞、运动和电路功能中的角色来解决行为中中间神经元群体功能的基本问题。通过提供神经控制运动的基本信息，这项工作提供了关于中间神经元群体如何共同发挥作用以协调运动的信息基础。这项工作对于理解由损伤和疾病造成的运动障碍的神经基础至关重要。

DESCRIPTION (provided by applicant): Most vertebrate behaviors depend on the coordinated activity of many neurons in the brain and/or spinal cord. While the organization and function of single iterations of spinal cord circuits have been examined, it is unknown how interneuron populations distributed across segments generate functional behaviors. The goal of this research is to examine the longitudinal distribution of spinal cord interneurons and the roles of those interneuron populations in behavior. This work takes advantage of novel techniques for neuron imaging in the larval zebrafish model system, including cell population activity imaging and cell-specific ablation techniques, to test hypotheses of interneuron organization and function. Aim 1 examines the longitudinal distributions of spinal cord interneurons testing the hypothesis that there is a rostrocaudal gradient in cell and population size of descending interneurons in motor circuits. Aim 2 determines the roles of descending interneurons in behavior. Cell-specific lesioning is used to remove a population of interneurons and behavior is assessed before and after those ablations. Aim 2 tests the hypotheses that removing descending excitatory interneurons will decrease bending amplitude, angular velocity, angular acceleration and, for rhythmic movements, disrupt the pattern of axial wave propagation. This is the first test of the roles of spinal interneurons in vertebrates. Aim 3 bridges Aim 1 and Aim 2 to address how interneurons effect their behavioral roles by imaging cell activity across a population of neurons downstream of the ablated cells. We hypothesize that ablating excitatory startle interneurons will decrease activity of interneurons and motoneurons in the ablation region in proportion to the number of ablated cells but will not alter caudal activity. We hypothesize that that ablating excitatory swim interneurons will decrease interneuron activity in and caudal to the region of the ablations. The aims of this proposal address fundamental questions about interneuron population function in behaviors by testing the roles cells and in movement and in circuit function. By providing basic information on the neural control of movements, this work provides a foundation of information on how populations of interneurons function together to coordinate movement. Such work is critical for understanding the neural basis of movement disruption through injury and disease.