Analysis of the recurrent Renshaw circuit

描述（由申请人提供）：在开发伴随脊柱损伤和神经系统疾病的运动功能障碍的治疗方法时，对脊柱系统的组织和功能的了解是一个关键需求。为了实现这一目标，本申请的长期目标是确定运动神经元池在运动活动期间是如何协调和调节的。本申请的具体目的是基于这样的提议，即Renshaw复发性抑制调节由脊髓模式发生器产生的共同兴奋性驱动共激活的运动神经元和相关la中间神经元的组的活性。将通过检验两个假设来探讨这种可能性。第一个具体目标的研究将测试这一假设，即运动和抓挠过程中的节律性运动命令分布到运动核团及其相关的相互抑制性中间神经元。实验支持这一假设将建立一个平行分布的节奏驱动信号的运动神经元和相关的la中间神经元作为一个基本特征，在组织的脊髓模式发生器。第二个具体目标的研究将测试这一假设，即由脊髓网络产生的有节奏的运动命令被组织起来，以维持对运动核团的单独兴奋性驱动，这些运动核团支配拮抗肌，并通过相互抑制联系起来。相互抑制是运动神经元、相互抑制性中间神经元和Renshaw细胞的脊髓组织的共同特征，然而脊髓模式的产生可以涉及运动核的共激活，其肌肉是机械拮抗剂以及相互激活。我们建议，这些抑制性网络的充分控制的条件和需要在生产运动模式的适应性都得到满足，限制运动神经元的预测，从个别集的模式生成神经元池，不包括这些相互抑制连接。计划中的研究将提供有关参与模式生成和运动控制的脊髓网络组织的基本信息。此外，所获得的信息将深入了解脊髓机制在脊髓损伤和神经系统疾病后运动功能障碍中的作用，并将有助于指导治疗这些疾病的疗法的开发，例如在脊髓损伤后使用脊髓刺激。

DESCRIPTION (provided by applicant): Knowledge of the organization and function of spinal systems is a critical need in developing therapies for motor dysfunction that accompany spinal injury and neurological disease. To achieve this goal, the longrange objective of this application is to determine how motoneuron pools are coordinated and regulated during motor activities. The specific aims of this application are based on the proposal that Renshaw recurrent inhibition regulates the activity of sets of motoneurons and associated la interneurons coactivated by common excitatory drives produced by spinal pattern generators. This possibility will be explored by testing two hypotheses. Studies for the first specific aim will test the hypothesis that rhythmic motor commands during locomotion and scratching are distributed to motor nuclei and their associated la reciprocal inhibitory interneurons. Experimental support for this hypothesis would establish a parallel distribution of rhythmic drive signals to motoneurons and associated la interneurons as a fundamental feature in the organization of spinal pattern generators. Studies for the second specific aim will test the hypothesis that rhythmic motor commands generated by spinal networks are organized to maintain separate excitatory drives to motor nuclei that innervate antagonist muscles and that are linked by la reciprocal inhibition. Reciprocal inhibition is a common feature of the spinal organization of motoneurons, la reciprocal inhibitory interneurons and Renshaw cells, yet spinal pattern generation can involve coactivation of motor nuclei whose muscles are mechanical antagonists as well as reciprocal activation. We propose that conditions for adequate control by these reciprocally inhibitory networks and the need for such adaptability in producing motor patterns are both satisfied by restricting motoneuron projections from individual sets of pattern generating neurons to pools that do not include these reciprocal inhibitory connections. The planned studies will provide fundamental information concerning the organization of spinal networks involved in pattern generation and motor control. In addition, the information obtained will provide insight into the roles that spinal mechanisms play in motor dysfunction following spinal injury and neurological disease and will help guide the development of therapies for the treatment of these disorders, such as the use of spinal cord stimulation following spinal injury.