Analysis of the recurrent Renshaw circuit

描述（由申请人提供）：了解脊髓系统的组织和功能是开发伴随脊髓损伤和神经系统疾病的运动功能障碍治疗的关键需求。为了实现这一目标，本应用程序的长期目标是确定运动神经元池在运动活动期间如何协调和调节。该应用的具体目的是基于Renshaw复发抑制调节运动神经元和相关中间神经元的活动，这些神经元由脊髓模式发生器产生的共同兴奋驱动共同激活。我们将通过测试两个假设来探讨这种可能性。第一个特定目的的研究将检验运动和抓抓过程中的节律性运动命令分布到运动核及其相关的互反抑制中间神经元的假设。对这一假设的实验支持将确立节律驱动信号平行分布到运动神经元和相关的中间神经元，作为脊髓模式发生器组织的基本特征。第二个特定目标的研究将检验这样一种假设，即由脊髓网络产生的有节奏的运动命令被组织起来，以维持对支配拮抗器肌肉的运动核的单独兴奋驱动，并通过相互抑制联系在一起。相互抑制是运动神经元、相互抑制中间神经元和Renshaw细胞的脊髓组织的共同特征，然而脊髓模式的产生可能涉及运动核的共激活，其肌肉是机械拮抗剂以及相互激活。我们提出，通过限制运动神经元从产生模式的单个神经元集投射到不包括这些相互抑制连接的池，可以满足这些相互抑制网络充分控制的条件和产生运动模式的这种适应性的需要。计划中的研究将提供有关参与模式产生和运动控制的脊髓网络组织的基本信息。此外，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的运动功能障碍中的作用，并将有助于指导这些疾病的治疗方法的发展，例如脊髓损伤后脊髓刺激的使用。

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.