article published yes Olena Kim author 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 Yuji Okamoto author 3337E116-F248-11E8-B48F-1D18A9856A870000-0003-0408-6094 Walter Kaufmann author 3F99E422-F248-11E8-B48F-1D18A9856A870000-0001-9735-5315 Nils Brose author Ryuichi Shigemoto author 499F3ABC-F248-11E8-B48F-1D18A9856A870000-0001-8761-9444 Peter M Jonas author 353C1B58-F248-11E8-B48F-1D18A9856A870000-0001-5001-4804 PeJo department EM-Fac department RySh department Biophysics and circuit function of a giant cortical glutamatergic synapse project Synaptic communication in neuronal microcircuits project Mechanisms of GABA release in hippocampal circuits project Structural & functional basis of presynaptic plasticity project Zellkommunikation in Gesundheit und Krankheit project FWF Open Access Fund project It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse. https://research-explorer.ista.ac.at/download/18603/18608/2024_PloSBio_Kim.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Public Library of Science2024 eng 1544-9173 1545-7885 39556620 00135856870000310.1371/journal.pbio.3002879 2211 https://research-explorer.ista.ac.at/record/18296 Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. 22(11), e3002879. O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,” <i>PLoS Biology</i>, vol. 22, no. 11. Public Library of Science, 2024. Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” <i>PLoS Biology</i>, vol. 22, no. 11, e3002879, Public Library of Science, 2024, doi:<a href="https://doi.org/10.1371/journal.pbio.3002879">10.1371/journal.pbio.3002879</a>. Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., &#38; Jonas, P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. <i>PLoS Biology</i>. Public Library of Science. <a href="https://doi.org/10.1371/journal.pbio.3002879">https://doi.org/10.1371/journal.pbio.3002879</a> Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto, and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” <i>PLoS Biology</i>. Public Library of Science, 2024. <a href="https://doi.org/10.1371/journal.pbio.3002879">https://doi.org/10.1371/journal.pbio.3002879</a>. O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS Biology 22 (2024). Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. <i>PLoS Biology</i>. 2024;22(11). doi:<a href="https://doi.org/10.1371/journal.pbio.3002879">10.1371/journal.pbio.3002879</a> 186032024-12-01T23:01:54Z2025-10-15T06:31:50Z