The demonstration that inhibition of PKA leads to a large increase in quantal size suggests that there is a high basal phosphorylation of DGluRIIA at the wild-type synapse. The PKA-dependent reduction in quantal size is accompanied developmentally by an increase in presynaptic quantal content, indicating the presence of a retrograde signal that regulates presynaptic release. During the development of the Drosophila NMJ, a large increase in muscle volume is tightly coupled to increases in both presynaptic structure and presynaptic function. This coupling assures that the presynaptic motoneuron is able to appropriately excite postsynaptic muscle. The hypothesis that an activity-dependent retrograde signal regulates presynaptic release at this synapse is supported by the data.
Quantal content is a measure of the number of vesicles released by the nerve.
This increase in quantal content is observed in each of the three experimental genotypes in which the PKA activator decreases quantal size. Since presynaptic release is increased in response to a decrease in the postsynaptic sensitivity to transmitter, it is proposed that there exists a retrograde signal capable of regulating presynaptic transmitter release at this synapse. The PKA-dependent increase in quantal size due to PKA inhibition is not compensated for by a change in presynaptic release, however. PKA activity was inhibited in muscle by expression of a mutant PKA regulatory subunit under UAS control. These regulatory subunits carry a mutated cAMP binding site and as a result have reduced sensitivity to cAMP resulting in decreased PKA catalytic activity.