Dynamics of a neural circuit that coordinates locomotion

描述(申请人提供)：这项研究的目标是从细胞的角度了解中枢神经系统(CNS)在正常运动中如何协调不同肢体的运动。由于其模块化的节段性组织，小龙虾游泳网系统提供了在细胞条件下分析协调不同肢体运动的神经机制的机会。在控制游泳者的四对局部回路中，每一对都出现了三个不同的协调中间神经元，总共有12对神经元。这些神经元中的每一个都将轴突投射到中枢神经系统的其他部分。当中枢神经系统活跃地表达游泳者运动模式时，这些中间神经元中的每一个在每个周期的特定阶段都会发射一次脉冲爆发。这些神经元中的棘波对于正常的节段间协调既是必要的，也是充分的。 这些协调轴突与其他节段的局部连合中间神经元突触，形成节间神经回路。我们将研究控制一段肢体的局部回路的状态信息是如何由这些协调神经元编码的，并由控制其他肢体的回路再次解码的。这项建议的具体目标是： 1.发现单个协调中间神经元是否独立编码信息，或者不同轴突的相关放电是否传达重要信息。 2.描述作为协调轴突直接靶点的局部连合神经元对协调信息的转化。 3.检验该协调电路的两个细胞模型的假设，并扩展这些模型以纳入新的实验结果。 这些研究项目将使用同步细胞外记录协调轴突和肢体运动输出的棘波，以及分离的小龙虾中枢神经系统中协调神经元和连合神经元的微电极记录。它们还需要激光共聚焦显微镜，以及电路动力学的计算分析。这项研究将成为研究其他动物运动过程中肢体协调的模型，包括对哺乳动物运动至关重要的脊髓回路，包括人类。

DESCRIPTION (provided by applicant): The goal of this research is to understand in cellular terms how a central nervous system (CNS) coordinates the movements of different limbs during normal locomotion. Because of its modular segmental organization, the crayfish swimmeret system presents the opportunity to analyze in cellular terms the neural mechanisms that coordinate movements of different limbs. Three different coordinating interneurons arise in each of the four pairs of local circuits that control swimmerets, twelve pairs of neurons in all. Each of these neurons projects its axon to other segments in the CNS. When the CNS is actively expressing the swimmeret motor pattern, each of these interneurons fires a burst of impulses at a characteristic phase in each cycle. These spikes in these neurons are both necessary and sufficient for normal intersegmental coordination. These coordinating axons synapse with local commissural interneurons in other segments to form an intersegmental neural circuit. We will investigate how information about the state of the local circuit controlling a limb on one segment is encoded by these coordinating neurons and decoded again by the circuits that control other limbs. The Specific Aims of this proposal are: 1. To discover whether individual coordinating interneurons encode information independently, or whether correlated firing in different axons conveys important information. 2. To describe the transformation of coordinating information by local commissural neurons that are direct targets of coordinating axons. 3. To test assumptions of two cellular models of this coordinating circuit and to extend these models to incorporate new experimental results. These research projects will use simultaneous extracellular recording of spikes in coordinating axons and the motor output to sets of limbs, and microelectrode recording from coordinating neurons and commissural neurons in isolated crayfish CNS. They also require laser confocal microscopy, and computational analysis of circuit dynamics. This research will be a model for study of limb coordination during locomotion in other animals, including the spinal circuits that are critical to locomotion in mammals, including man.