GENETIC-ANALYSIS OF GLUTAMATE RECEPTORS IN DROSOPHILA REVEALS A RETROGRADE SIGNAL REGULATING PRESYNAPTIC TRANSMITTER RELEASE

Postsynaptic sensitivity to glutamate was genetically manipulated at t he Drosophila neuromuscularjunction (NMJ) to test whether postsynaptic activity can regulate presynaptic function during development. We clo ned the gene encoding a second muscle-specific glutamate receptor, DGl uRIIB, which is closely related to the previously identified DGluRIIA and located adjacent to it in the genome. Mutations that eliminate DGl uRIIA (but not DGluRIIB) or transgenic constructs that increase DGluRI IA expression were generated. When DGluRIIA is missing, the response o f the muscle to a single vesicle of transmitter is substantially decre ased.;However, the response of the muscle to nerve stimulation is norm al because quantal content is significantly increased. Thus, a decreas e in postsynaptic receptors leads to an increase in presynaptic transm itter release, indicating that postsynaptic activity controls a retrog rade signal that regulates presynaptic function.