Genes required for GABA function in Caenorhabditis elegans

Abstract

gamma-Aminobutyric acid (GABA) neurotransmission is widespread in vertebrate and invertebrate nervous systems. Here we use a genetic approach to identify molecules specific to GABA function. On the basis of the known in vivo roles of GABAergic neurons in controlling behaviour of the nematode Caenorhabditis elegans, we identified mutants defective in GABA-mediated behaviours. Five genes are necessary either for GABAergic neuronal differentiation or for pre- or postsynaptic GABAergic function. The gene unc-30 is required for the differentiation of a specific 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-46 and unc-47 seem to be required for normal GABA release. Finally, the gene unc-49 is apparently necessary postsynaptically for the inhibitory effect of GABA on the body muscles and might encode a protein needed for the function of a GABAA-like receptor. Some of these genes are likely to encode previously unidentified proteins required for GABA function.

Electrical activity and behavior in the pharynx of caenorhabditis elegans

“…Other genes with an established role in neurotransmission are those involved with synthesis and response to γ-aminobutyric acid (GABA), one of the principal inhibitory neurotransmitters in C. elegans (Mcintire et al, 1993a). GABA immunoreactivity is not seen in the pharynx (McIntire et al, 1993b), and mutants defective in GABAergic transmission have no obvious detect in pumping (unpublished data).…”

“…GABA immunoreactivity is not seen in the pharynx (McIntire et al, 1993b), and mutants defective in GABAergic transmission have no obvious detect in pumping (unpublished data). Nevertheless, it remains possible that some inhibitory pharyngeal neuron uses GABA since there are GABA immunoreactive neurons in the pharynx of the parasitic nematode Ascaris (Guastella et al, 1991) and since the GABA agonist muscimol has an inhibitory effect on pharyngeal pumping which is dependent on the unc-49 gene product, a likely component of a GABA postsynaptic receptor (Mcintire et al, 1993a). To test whether GABA is the M3 neurotransmitter, we recorded from worms mutant for unc-49 or for unc-25, a gene necessary for the synthesis of GABA (Mcintire et al, 1993a).…”

“…Serotonin (10 mM) was included in the bath to stimulate pumping. (B) EPG of a worm mutant for unc-49, a gene necessary for the inhibitory effect of the GABA agonist muscimol on pharyngeal pumping (McIntire et al, 1993a). P phase transients are present.…”

“…P phase transients are present. (C) EPG of a worm mutant for unc-25, a gene necessary for the synthesis of GABA (McIntire et al, 1993a). P phase transients are present.…”

TheCaenorhabditis elegans snf-11Gene Encodes a Sodium-dependent GABA Transporter Required for Clearance of Synaptic GABA

“…Bar, 10 m. Jin et al (1999). This same set of 26 cells also express the UNC-47 vesicular GABA transporter (McIntire et al, 1997) and contain GABA (McIntire et al, 1993a). b Not listed in class 3 are four unidentified cells, two in the head and two in the retrovesicular ganglion (see Figure 5).…”