Presynaptic Mechanism Underlying cAMP-Dependent Synaptic Potentiation

Abstract

The adenylyl cyclase activator forskolin presynaptically facilitates synaptic transmission at many synapses, but the exact intracellular mechanism underlying this effect is not known. We studied this issue at the calyx of Held, where it is possible to make simultaneous presynaptic and postsynaptic whole-cell recordings. Bath application of forskolin or intracellular application of cAMP into presynaptic terminals strongly potentiated EPSCs. The forskolin-induced synaptic potentiation was associated with increases in release probability (P) and number of releasable synaptic vesicles (N). Forskolin had no effect on the peak amplitudes of presynaptic Ca²⁺ currents or K⁺ currents, suggesting that the main target of cAMP resides in downstream of Ca²⁺ influx. Intracellular application of the selective Epac agonist 8-(4-chlorophenylthio)-2′-O-methyl-cAMP into presynaptic terminals potentiated EPSCs, suggesting that Epac is the main target of cAMP-induced synaptic potentiation. We conclude that an increase in cAMP concentration in the nerve terminal facilitates transmitter release by increasing both release probability and number of releasable vesicles via activating the Epac pathway at the calyx of Held.