Analysis of the recurrent Renshaw circuit

描述(申请人提供)：脊柱系统的组织和功能的知识是开发治疗伴随脊髓损伤和神经疾病的运动功能障碍的关键需要。为了实现这一目标，这项应用的长期目标是确定运动活动期间运动神经元池是如何协调和调节的。这一应用的具体目的是基于这样的建议，即Renshaw反复抑制调节由脊髓模式生成器产生的共同兴奋驱动共同激活的运动神经元和相关的LA中间神经元的活动。这种可能性将通过检验两个假设来探索。对第一个特定目标的研究将检验这样一个假设，即运动和抓挠过程中有节奏的运动指令分布到运动核团及其相关的相互抑制中间神经元。对这一假说的实验支持将建立到运动神经元和相关的LA中间神经元的节律性驱动信号的平行分布，作为脊髓模式生成器组织的基本特征。对第二个特定目的的研究将检验这样一个假设，即由脊髓网络产生的有节奏的运动指令被组织起来，以维持对支配拮抗肌肉的运动核团的单独的兴奋性驱动，这些运动核团通过LA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，但脊髓模式的产生可能涉及作为机械拮抗剂的肌肉的运动核团的共同激活以及相互激活。我们认为，这些相互抑制网络充分控制的条件和对产生运动模式的这种适应性的需要，都可以通过限制来自模式产生神经元的单个集合的运动神经元投射到不包括这些相互抑制联系的池中来满足。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，所获得的信息将有助于深入了解脊髓损伤和神经疾病后脊髓机制在运动功能障碍中所起的作用，并将有助于指导治疗这些疾病的治疗方法的发展，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.