Preferential potentiation of fast-releasing synaptic vesicles by cAMP at the calyx of Held

We have studied the effects of cAMP on synaptic transmission at the calyx o f Held and found that forskolin (an activator of adenylate cyclase) and 8-B r-cAMP (a membrane-permeable analog of cAMP) potentiated excitatory postsyn aptic currents (EPSCs). Direct sampling of miniature EPSCs (mEPSCs) and non stationary fluctuation analysis showed that mEPSCs were not modulated by cA MP, suggesting that the locus of modulation is presynaptic. Deconvolution w as used to examine effects of cAMP on quantal-release rates. By using this method, it was shown recently that release probabilities of readily releasa ble vesicles are heterogeneous. Here, we show that cAMP selectively increas es the number of vesicles with higher release probabilities, whereas a slow component of the EPSC, representing vesicles that fuse more slowly, is unc hanged. cAMP increases the apparent Ca2+ sensitivity for secretion, but thi s increase does not reflect an increase in release probability necessarily but rather an increase in the number of highly sensitive vesicles.