Central control of rhythmic movement in a vertebrate

描述（由申请人提供）：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迭代的组织和功能，但尚不清楚分布在各节段的中间神经元群如何产生功能行为。本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。这项工作利用了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，来测试中间神经元组织和功能的假设。目的1检查脊髓中间神经元的纵向分布，以验证运动回路中下行中间神经元的细胞和种群大小存在背-尾向梯度的假设。目的2确定下行中间神经元在行为中的作用。细胞特异性病变用于移除中间神经元群，并评估消融前后的行为。目的2验证了去除下行兴奋性中间神经元会降低弯曲幅度、角速度、角加速度的假设，并且对于有节奏的运动，会破坏轴波传播模式。这是对脊椎动物脊髓中间神经元作用的首次测试。目的3连接目的1和目的2，通过在消融细胞下游的神经元群体中成像细胞活动来解决中间神经元如何影响其行为作用。我们假设，消融兴奋性惊吓中间神经元会使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地减少，但不会改变尾侧活动。我们假设消融兴奋性游泳中间神经元会降低消融区域和尾侧的中间神经元活动。本研究的目的是通过测试细胞在运动和电路功能中的作用来解决关于中间神经元群体在行为中的功能的基本问题。通过提供运动神经控制的基本信息，这项工作为研究中间神经元群体如何协同运动提供了基础信息。这项工作对于理解损伤和疾病导致运动中断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.