Yao Mingchen, Nagamori Akira, Campos Maçãs Sandrina, Azim Eiman, Sharpee Tatyana, Goulding Martyn, Golomb David, Gatto Graziana
Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA; Department of Physics, UCSD, La Jolla, CA, USA.
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Cell Rep. 2025 Jun 17;44(6):115845. doi: 10.1016/j.celrep.2025.115845.
Rhythmic motor behaviors are generated by neural networks termed central pattern generators (CPGs). Although locomotor CPGs have been extensively characterized, it remains unknown how the neuronal populations composing them interact to generate adaptive rhythms in mammals. We explored the cooperation dynamics among the three main populations of ipsilaterally projecting spinal CPG neurons-V1, V2a, and V2b neurons-in scratch reflex rhythmogenesis. Individual ablation of the three neuronal populations reduced the oscillation frequency. Activation of excitatory V2a neurons enhanced the oscillation frequency, while activating inhibitory V1 neurons suppressed movement. Building on these findings, we developed a neuromechanical model made of self-oscillating flexor and extensor modules coupled via inhibition. Rhythm frequency is increased by strong intra-module inhibition and facilitation mechanisms in excitatory neurons and decreased by strong inter-module inhibition. In sum, we describe how genetically identified neuron types and the strengths of their synaptic connections drive scratch rhythmogenesis.
节律性运动行为由称为中枢模式发生器(CPG)的神经网络产生。尽管运动CPG已得到广泛表征,但构成它们的神经元群体如何相互作用以在哺乳动物中产生适应性节律仍不清楚。我们探索了同侧投射脊髓CPG神经元的三个主要群体——V1、V2a和V2b神经元——在搔抓反射节律发生中的合作动态。对这三个神经元群体进行单独消融会降低振荡频率。兴奋性V2a神经元的激活增强了振荡频率,而激活抑制性V1神经元则抑制了运动。基于这些发现,我们开发了一个神经力学模型,该模型由通过抑制耦合的自振荡屈肌和伸肌模块组成。节律频率通过兴奋性神经元中强大的模块内抑制和易化机制而增加,并通过强大的模块间抑制而降低。总之,我们描述了基因鉴定的神经元类型及其突触连接强度如何驱动搔抓节律的发生。