Proceedings of the National Academy of Sciences
Rapid Ca2+ channel accumulation contributes to cAMP-mediated increase in transmission at hippocampal mossy fiber synapses
Fukaya, R., Maglione, M., Sigrist, S. J., & Sakaba, T.
synapse, synaptic transmission, synaptic plasticity, calcium channels, hippocampal mossy fiber
Despite the importance of the activation of the cAMP/PKA signaling pathway for presynaptic modulation, its cellular and molecular mechanisms remain unclear. In this study, we tackled this issue at hippocampal mossy fiber-CA3 synapses by combining paired electrophysiological recordings, Ca2+ uncaging, total internal reflection fluorescence (TIRF) microscopy for direct measurements of presynaptic active zone Ca2+ influx, and superresolution time-gated STED microscopy for visualization of Ca2+ channel clusters within active zones. Our results suggest that Ca2+ channels near release sites might accumulate upon activation of the cAMP/PKA pathway in the time scale of only several minutes. Our findings may thus change the focus from release machinery to Ca2+ channel clusters and their dynamics as a cell biological mechanism of cAMP-dependent synaptic modulation.