Presynaptic glutamic acid decarboxylase is required for induction of the postsynaptic receptor field at a glutamatergic synapse

We have systematically screened EMS-mutagenized Drosophila for embryonic le thal strains with defects in glutamatergic synaptic transmission. Surprisin gly, this screen led to the identification of several alleles with missense mutations in highly conserved regions of Dgad1. Analysis of these gad muta nts reveals that they are paralyzed owing to defects in glutamatergic trans mission at the neuromuscular junction. Further electrophysiological and imm unohistochemical examination reveals that these mutants have greatly reduce d numbers of postsynaptic glutamate receptors in an otherwise morphological ly normal synapse. By overexpressing wild-type Dgad1 in selected neurons, w e show that GAD is specifically required in the presynaptic neuron to induc e a postsynaptic glutamate receptor field,and that the level of postsynapti c receptors is closely dependent on presynaptic GAD function. These data de monstrate that GAD plays an unexpected role in glutamatergic synaptogenesis .