The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylaseand is required for synaptic transmission but not synaptic development

The neurotransmitter GABA has been proposed to play a role during nervous s ystem development. We show that the Caenorhabditis elegans gene unc-25 enco des glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme. unc-25 is expressed specifically in GABAergic neurons. Null mutations in unc-25 e liminate the UNC-25 protein or alter amino acids conserved in all known GAD s, result in a complete lack of GABA, and cause defects in all GABA-mediate d behaviors. In unc-25 mutants the GABAergic neurons have normal axonal tra jectories and synaptic connectivity, and the size and shape of synaptic ves icles are normal. The number of synaptic Vesicles at GABAergic neuromuscula r junctions is slightly increased. Cholinergic ventral nerve cord neurons, which innervate the same muscles as GABAergic ventral cord neurons, have no rmal morphology, connectivity, and synaptic vesicles. We conclude that GAD activity and GABA are not necessary for the development or maintenance of n euromuscular junctions in C. elegans.