Syed Durafshan Sakeena, Ravbar Primoz, Simpson Julie H
Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
Lead Contact.
bioRxiv. 2025 Feb 11:2024.06.05.597468. doi: 10.1101/2024.06.05.597468.
Limbs execute diverse actions coordinated by the nervous system through multiple motor programs. The basic architecture of motor neurons that activate muscles which articulate joints for antagonistic flexion and extension movements is conserved from flies to vertebrates. While excitatory premotor circuits are expected to establish sets of leg motor neurons that work together, our study uncovered an instructive role for inhibitory circuits - including their ability to generate rhythmic leg movements. Using electron microscopy data in the nerve cord, we categorized ~120 GABAergic inhibitory neurons from the 13A and 13B hemilineages into classes based on similarities in morphology and connectivity. By mapping their connections, we uncovered pathways for inhibiting specific groups of motor neurons, disinhibiting antagonistic counterparts, and inducing alternation between flexion and extension. We tested the function of specific inhibitory neurons through optogenetic activation and silencing, using high resolution quantitative analysis of leg movements during grooming. We combined findings from anatomical and behavioral analyses to construct a computational model that can reproduce major aspects of the observed behavior, confirming sufficiency of these premotor inhibitory circuits to generate rhythms.
肢体通过多个运动程序执行由神经系统协调的各种动作。激活用于拮抗屈伸运动的关节肌肉的运动神经元的基本结构从苍蝇到脊椎动物都是保守的。虽然兴奋性运动前电路预计会建立协同工作的腿部运动神经元组，但我们的研究发现了抑制性电路的指导作用——包括它们产生有节奏腿部运动的能力。利用神经索中的电子显微镜数据，我们根据形态和连接的相似性，将来自13A和13B半谱系的约120个GABA能抑制性神经元分类。通过绘制它们的连接，我们发现了抑制特定运动神经元组、解除拮抗对应神经元抑制以及诱导屈伸交替的途径。我们通过光遗传学激活和沉默，利用梳理过程中腿部运动的高分辨率定量分析，测试了特定抑制性神经元的功能。我们结合解剖学和行为分析的结果，构建了一个计算模型，该模型可以重现观察到的行为的主要方面，证实了这些运动前抑制性电路产生节律的充分性。
