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bioRxiv · 10.64898/2026.04.10.717587

A circuit-to-muscle signaling axis controls locomotor gait transitions in C. elegans

Moon, K. M.·Cho, J.·Kim, J.·Kim, K.
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Abstract

Animals switch between locomotor gaits to adapt to changing environments, yet how defined neural circuits and genes coordinate gait transitions remains poorly understood. Here, we show that the head motor neuron SMB acts as a critical gating node that enables the transition from crawling to swimming in Caenorhabditis elegans. SMB ablation disrupts head-body synchronization, prolongs muscle activation, and impairs curvature switching during swimming, indicating that the SMB neurons function to constrain motor output to stabilize swimming-specific oscillations. Through an unbiased forward genetic screen, we identify the NALCN channel complex component UNC-79 and the muscle nicotinic acetylcholine receptor subunit UNC-29 as key molecular determinants of gait transition. UNC-79 functions across multiple head interneuron modules to stabilize circuit-wide excitability required for sustained swimming, whereas UNC-29 acts cell-autonomously in body wall muscles to refine calcium amplitude and propagation dynamics. Genetic epistasis analyses position the SMB neurons upstream of UNC-29-mediated muscle activation, establishing a circuit-to-muscle signaling axis that links defined head motor neurons to downstream molecular effectors. Together, our findings show that gait transition emerges from coordinated modulation of neuronal excitability and muscle calcium dynamics, providing a mechanistic framework for how neural circuits reconfigure motor states to adapt locomotor behavior. HIGHLIGHTSO_LIThe SMB head motor neurons govern the crawl-to-swim transition C_LIO_LIUNC-79/NALCN stabilizes circuit excitability for sustained swimming C_LIO_LIMuscle nAChR subunit UNC-29 tunes calcium gain during gait transition C_LIO_LIA circuit-to-muscle pathway coordinates locomotor state transition C_LI IN BRIEFGait transitions require coordinated changes in neural circuit activity and muscle output. Moon et al. show that the SMB head motor neurons regulate the switch from crawling to swimming in C. elegans by coupling distributed circuit excitability to muscle calcium gain control, defining a circuit-to-muscle pathway that stabilizes locomotor state transitions.

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Moon, K. M., Cho, J., Kim, J., Kim, K.. 2026-04-14. A circuit-to-muscle signaling axis controls locomotor gait transitions in C. elegans. https://doi.org/10.64898/2026.04.10.717587

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