Excitatory GABA receptors shape locomotor circuit organization in C. elegans.

Caenorhabditis elegans encodes 102 cys-loop ligand-gated ion channels (LGICs) via the lgc gene family, including excitatory γ-aminobutyric acid (GABA) receptors not found in vertebrates. Although GABA is classically inhibitory, in C. elegans it can also elicit excitation. However, how those excitatory GABA receptors are organized within motor circuits remains poorly understood. Using publicly available single-cell transcriptomic datasets, we found that lgc genes are broadly enriched in locomotion motor neurons, largely driven by GABA receptor–encoding members. Among these, LGC-35 and EXP-1—both excitatory GABA receptors—exhibit subtype-specific and spatially biased expression patterns. A-type motor neurons, which mediate backward locomotion, display striking posterior enrichment of lgc-35 and exp-1, whose largely non-overlapping distributions suggest distinct functional roles. Connectomic analysis, which reconstructs synaptic connections from C. elegans whole-animal electron microscopy data, reveals direct GABAergic input from D-type to A-type motor neurons, suggesting that GABA from D-type neurons excites A-type neurons to regulate backward locomotion. These findings revise classical inhibitory-centric models of GABAergic locomotor control and highlight the role of excitatory GABA signaling in directionally precise motor output.