Developmental regulation of glutamate receptor field size by nonvesicular glutamate release.

We hypothesized that presynaptic glutamate regulates postsynaptic ionotropic glutamate receptor number during synaptogenesis. To test this idea, we genetically manipulated presynaptic glutamate levels at the glutamatergic Drosophila neuromuscular junction (NMJ), then microscopically and electrophysiologically measured postsynaptic glutamate receptor field size and function. Our data show that presynaptic glutamate is a strong negative regulator of postsynaptic receptor field size and function during development. Glutamate-triggered receptor downregulation was not affected by block of synaptic vesicle fusion, demonstrating that receptors are regulated by nonvesicular glutamate release. Our results reveal an elegant mechanism for receptor field regulation during synaptogenesis and reveal a nonpathological role for nonvesicular glutamate release at the synapse.