# Immature Caenorhabditis elegans motor neurons control early embryo behavior via both synaptic and nonsynaptic GABA release

## TL;DR

Immature neurons in C. elegans embryos use nonsynaptic GABA release to control early movement before synapses form.

## Contribution

The study reveals that nonsynaptic GABA release from immature motor neurons regulates embryo behavior before synapse formation.

## Key findings

- Early embryo motion inhibition in C. elegans is caused by immature GABAergic motor neurons.
- Nonsynaptic GABA mechanisms predominate over synaptic ones in controlling early embryo behavior.
- Motion inhibition requires GABA synthesis in DD neurons and GABAA receptors in muscles.

## Abstract

Little is known about how prenatal circuits control embryo behavior. We show that the motion of early Caenorhabditis elegans embryos is transiently inhibited by immature GABAergic motor neurons that have not yet completed neurite outgrowth. GABA’s inhibitory effect on early embryo behavior occurs before most synapses have formed in the worm’s central neuropil. For this early behavior, we find that synaptic GABA release plays a minor role while nonsynaptic mechanisms predominate. Our results suggest that nonsynaptic forms of GABA transmission play a significant role in prenatal circuits.

Prenatal brain activity has long lasting effects on subsequent neurodevelopment. It is unclear if early brain activity is dominated by cell intrinsic, synaptic, or nonsynaptic mechanisms. We address this question by analyzing Caenorhabditis elegans embryo behavior in snf-11 mutants, which lack a plasma membrane GABA reuptake pump (orthologous to GAT1). At 510 to 570 min postfertilization, 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.