Immature C. elegans motor neurons control early embryo behavior via both synaptic and non-synaptic GABA release

Marvel-Coen, J.; Ardiel, E. L.; Zhao, J.; Nurrish, S.; Kaplan, J. M.

doi:10.1101/2025.11.19.689106

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bioRxiv · 10.1101/2025.11.19.689106

Immature C. elegans motor neurons control early embryo behavior via both synaptic and non-synaptic GABA release

Marvel-Coen, J.·Ardiel, E. L.·Zhao, J.·Nurrish, S.·Kaplan, J. M.

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Abstract

Pre-natal brain activity has long lasting effects on subsequent neurodevelopment. It is unclear if early brain activity is dominated by cell intrinsic, synaptic, or non-synaptic mechanisms. We address this question by analyzing C. elegans embryo behavior in snf-11 mutants, which lack a plasma membrane GABA re-uptake pump (orthologous to GAT1). At 510-570 minutes post-fertilization, embryo motion was transiently and potently inhibited in snf-11 GAT1 mutants, which precedes formation of most nerve ring synapses. This transient motion inhibition requires GABA synthesis in DD motor neurons and UNC-49 GABAA receptors in body muscles. When motion inhibition occurs, DD neurons have not yet completed neurite outgrowth. Genetic analysis suggests that motion inhibition was mediated by both synaptic and tonic GABA release from DD motor neurons. These results suggest that DD neurons control embryo behavior prior to completing their developmental maturation. Significance StatementLittle is known about how prenatal circuits control embryo behavior. We show that the motion of early C. elegans embryos is transiently inhibited by immature GABAergic motor neurons that have not yet completed neurite outgrowth. GABAs inhibitory effect on early embryo behavior occurs before most synapses have formed in the worms central neuropil. For this early behavior, we find that synaptic GABA release plays a minor role while non-synaptic mechanisms predominate. Our results suggest that non-synaptic forms of GABA transmission play a significant role in prenatal circuits.

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Marvel-Coen, J., Ardiel, E. L., Zhao, J., Nurrish, S., Kaplan, J. M.. 2025-11-19. Immature C. elegans motor neurons control early embryo behavior via both synaptic and non-synaptic GABA release. https://doi.org/10.1101/2025.11.19.689106

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