Visualization of cyclic AMP-regulated presynaptic activity at cerebellar granule cells.

Adenylyl cyclase (AC) modulation of vesicular cycling was visualized at cultured cerebellar granule cell synapses using the sequential uptake of antibodies directed against the intraluminal domain of synaptotagmin I. Vesicle recycling due to spontaneous transmitter release in the absence of action potentials was increased by the AC/protein kinase A (PKA) activators forskolin and CPT-cAMP. These effects were blocked by the PKA inhibitor Rp-cAMPs. Cyclic AMP elevation also induced new cycling at previously silent sites. Activation of L-AP4-sensitive mGluR reduced the cAMP/PKA enhancement at preexisting synapses downstream of both AC and calcium channels. Modulation of the turnover and the number of vesicular release sites provide one mechanism that may underlie cAMP-dependent cerebellar long-term potentiation.