Falcón Moya, RafaelPérez Rodríguez, MikelPrius Mengual, JoséAndrade Talavera, YunieskyArroyo García, Luis EnriquePérez Artés, RocíoMateos-Aparicio Moreno, PedroGuerra Gómes, SoniaOliveira, João FilipeFlores Álvarez, GonzaloRodríguez-Moreno, Antonio2025-04-032025-04-032020Falcón-Moya, R., Pérez-Rodríguez, M., Prius-Mengual, J. et al. Astrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development. Nat Commun 11, 4388 (2020). https://doi.org/10.1038/s41467-020-18024-410.1038/s41467-020-18024-4https://hdl.handle.net/10433/23722Presynaptic spike timing-dependent long-term depression (t-LTD) at hippocampal CA3-CA1 synapses is evident until the 3rd postnatal week in mice, disappearing during the 4th week. At more mature stages, we found that the protocol that induced t-LTD induced t-LTP. We characterized this form of t-LTP and the mechanisms involved in its induction, as well as that driving this switch from t-LTD to t-LTP. We found that this t-LTP is expressed presynaptically at CA3-CA1 synapses, as witnessed by coefficient of variation, number of failures, paired-pulse ratio and miniature responses analysis. Additionally, this form of presynaptic t-LTP does not require NMDARs but the activation of mGluRs and the entry of Ca2+ into the postsynaptic neuron through L-type voltage-dependent Ca2+ channels and the release of Ca2+ from intracellular stores. Nitric oxide is also required as a messenger from the postsynaptic neuron. Crucially, the release of adenosine and glutamate by astrocytes is required for t-LTP induction and for the switch from t-LTD to t-LTP. Thus, we have discovered a developmental switch of synaptic transmission from t-LTD to t-LTP at hippocampal CA3-CA1 synapses in which astrocytes play a central role and revealed a form of presynaptic LTP and the rules for its induction.application/pdfenAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/STDPHippocampusAstrocytesNMDA receptorsDevelopmental plasticityjournal articleopen access