Shevtsova Natalia A, Talpalar Adolfo E, Markin Sergey N, Harris-Warrick Ronald M, Kiehn Ole, Rybak Ilya A
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Physiol. 2015 Jun 1;593(11):2403-26. doi: 10.1113/JP270121.
Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V0D and excitatory V0V CINs and ipsilaterally projecting excitatory V2a interneurons were shown to secure left-right alternation at different locomotor speeds. We have developed computational models of neuronal circuits in the spinal cord that include left and right rhythm-generating centres interacting bilaterally via three parallel pathways mediated by V0D , V2a-V0V and V3 neuron populations. The models reproduce the experimentally observed speed-dependent left-right coordination in normal mice and the changes in coordination seen in mutants lacking specific neuron classes. The models propose an explanation for several experimental results and provide insights into the organization of the spinal locomotor network and parallel CIN pathways involved in gait control at different locomotor speeds.
Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0D ) and excitatory (V0V ) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0D and V0V CINs and V2a interneurons to left-right alternation of neural activity, switching gaits between the left-right alternating walking-like activity and the left-right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits.
哺乳动物脊髓左右两侧神经元活动的协调由几组轴突穿过中线的连合中间神经元（CIN）提供。基因鉴定的抑制性V0D和兴奋性V0V CIN以及同侧投射的兴奋性V2a中间神经元被证明在不同运动速度下确保左右交替。我们开发了脊髓神经元回路的计算模型，其中包括左右节律产生中心，它们通过由V0D、V2a - V0V和V3神经元群体介导的三条平行途径进行双侧相互作用。这些模型再现了正常小鼠实验观察到的速度依赖性左右协调以及缺乏特定神经元类别的突变体中协调的变化。这些模型对几个实验结果提出了解释，并深入了解了脊髓运动网络的组织以及参与不同运动速度步态控制的平行CIN途径。
哺乳动物的不同运动步态，如行走或奔跑，是由脊髓神经元回路中的协调活动产生的。脊髓左右两侧神经元活动的协调由轴突穿过中线的连合中间神经元（CIN）提供。在本研究中，我们构建并分析了两个脊髓运动回路的计算模型，该模型由左右节律发生器通过由不同CIN介导的几条神经元途径进行双侧相互作用组成。模型中纳入的CIN群体包括基因鉴定的V0 CIN的抑制性（V0D）和兴奋性（V0V）亚型以及兴奋性V3 CIN。该模型还包括同侧投射的兴奋性V2a中间神经元，其介导对V0V CIN的兴奋性驱动。所提出的网络架构和CIN连接性使模型能够紧密再现并为几个实验观察结果提出机制解释。这些现象包括：V0D和V0V CIN以及V2a中间神经元对神经活动左右交替的不同速度依赖性贡献、缺乏特定神经元类别的突变体中左右交替的行走样活动和左右同步的跳跃样模式之间的步态转换，以及屈肌和伸肌相位持续时间的速度依赖性不对称变化。这些模型深入了解了脊髓网络的架构以及平行抑制性和兴奋性CIN途径的组织，并为这些途径如何在不同运动速度下维持交替和同步步态提出了解释。这些模型对哺乳动物运动回路的神经组织和运作提出了可测试的预测。
