Calcineurin inhibition revealed that many of regulated active zone phosphosites are Calcineurin substrates. In addition, it was shown that, phosphorylation of critical phosphosites were downregulated upon CaMKII inhibition.Overall, our data suggest that upon the stimulation of nerve terminal activity of CaMKII, PKC, PKA, ERK1/2, CK2, PP2A, and Calcineurin is upregulated, whereas activity of CdK5, GSK-3, PP1 is downregulated. In conclusion, we propose a model in which Ca 2+ has a primary role in regulation of tightly interconnected network of kinases and phosphatases upon stimulation.