GENES REQUIRED FOR GABA FUNCTION IN CAENORHABDITIS-ELEGANS

Gamma-AMINOBUTYRIC acid (GABA) neurotransmission is widespread in vert ebrate and invertebrate nervous systems1. Here we use a genetic approa ch to identify molecules specific to GABA function. On the basis of th e known in vivo roles of GABAergic neurons in controlling behaviour of the nematode Caenorhabditis elegans2, we identified mutants defective in GABA-mediated behaviours. Five genes are necessary either for GABA ergic neuronal differentiation or for pre- or postsynaptic GABAergic f unction. The gene unc-30 is required for the differentiation of a spec ific type of GABAergic neuron, the type-D inhibitory motor neuron. The gene unc-25 is necessary for GABA expression and probably encodes the GABA biosynthetic enzyme glutamic acid decarboxylase. The genes unc-4 6 and unc-47 seem to be required for normal GABA release. Finally, the gene unc-49 is apparently necessary postsynaptically for the inhibito ry effect of GABA on the body muscles and might encode a protein neede d for the function of a GABA(A)-like receptor. Some of these genes are likely to encode previously unidentified proteins required for GABA f unction.