Zhang Yongning, Shi Yunzhu, Zeng Kanghua, Chen Lili, Gao Shangbang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, PR China.
Nat Commun. 2025 May 12;16(1):4405. doi: 10.1038/s41467-025-59668-4.
Stable movement and efficient motor transition are both crucial for animals to navigate their environments, yet the neural principles underlying these abilities are not fully understood. In free-moving Caenorhabditis elegans, sustained forward locomotion is occasionally interrupted by backward movements, which are believed to result from reciprocal inhibition between the interneurons AVB and AVA. Here, we discovered that hierarchical competing inhibition circuits stabilize spontaneous movement and ensure motor transition. We found that the modulatory interneuron PVP activated AVB to maintain forward locomotion while inhibiting AVA to prevent backward movement. Another interneuron, DVC activates AVA and forms a disinhibition circuit that inhibits PVP, thereby relieving PVP's inhibition of AVA and facilitating backward movement. Notably, these asymmetrical circuit motifs create a higher-order competing inhibition that likely sharpens the motor transition. We also identified cholinergic and glutamatergic synaptic mechanisms underlying these circuits. This study elucidates a key neural principle that controls motor stability in C. elegans.
稳定的运动和高效的运动转换对于动物在其环境中导航都至关重要，然而这些能力背后的神经原理尚未完全被理解。在自由移动的秀丽隐杆线虫中，持续的向前运动偶尔会被向后运动打断，据信这是由中间神经元AVB和AVA之间的相互抑制导致的。在这里，我们发现分层竞争抑制回路可稳定自发运动并确保运动转换。我们发现调节性中间神经元PVP激活AVB以维持向前运动，同时抑制AVA以防止向后运动。另一个中间神经元DVC激活AVA并形成一个去抑制回路，该回路抑制PVP，从而减轻PVP对AVA的抑制并促进向后运动。值得注意的是，这些不对称的回路基序产生了更高阶的竞争抑制，这可能会加剧运动转换。我们还确定了这些回路背后的胆碱能和谷氨酸能突触机制。这项研究阐明了控制秀丽隐杆线虫运动稳定性的关键神经原理。
