POSTSYNAPTIC PKA CONTROLS QUANTAL SIZE AND REVEALS A RETROGRADE SIGNAL THAT REGULATES PRESYNAPTIC TRANSMITTER RELEASE IN DROSOPHILA

Two distinct mechanisms regulate synaptic efficacy at the Drosophila n euromuscular junction (NMJ): a PKA-dependent modulation of quantal siz e and a retrograde regulation of presynaptic release. Postsynaptic exp ression of a constitutively active PKA catalytic subunit decreases qua ntal size, whereas overexpression of a mutant PKA regulatory subunit ( inhibiting PKA activity) increases quantal size. Increased PKA activit y also decreases the response to direct iontophoresis of glutamate ont o postsynaptic receptors. The PKA-dependent modulation of quantal size requires the presence of the muscle-specific glutamate receptor DGluR IIA, since PKA-dependent modulation of quantal size is lost in homozyg ous viable DGluRIIA(-) mutants. Furthermore, elevated postsynaptic PKA reduces the quantal amplitude and the time constant of miniature exci tatory junctional potential (mEJP) decay to values that are nearly ide ntical to those observed in DGluRIIA(-) mutants. The PKA-dependent red uction in quantal size is accompanied developmentally by an increase i n presynaptic quantal content, indicating the presence of a retrograde signal that regulates presynaptic release.