Astrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development

Rafael Falcón-Moya, Mikel Pérez-Rodríguez, José Prius-Mengual, Yuniesky Andrade-Talavera, Luis E. Arroyo-García, Rocío Pérez-Artés, Pedro Mateos-Aparicio, Sónia Guerra-Gomes, João Filipe Oliveira, Gonzalo Flores and Antonio Rodríguez-Moreno ()
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Rafael Falcón-Moya: Universidad Pablo de Olavide
Mikel Pérez-Rodríguez: Universidad Pablo de Olavide
José Prius-Mengual: Universidad Pablo de Olavide
Yuniesky Andrade-Talavera: Universidad Pablo de Olavide
Luis E. Arroyo-García: Universidad Pablo de Olavide
Rocío Pérez-Artés: Universidad Pablo de Olavide
Pedro Mateos-Aparicio: Universidad Pablo de Olavide
Sónia Guerra-Gomes: University of Minho
João Filipe Oliveira: University of Minho
Gonzalo Flores: Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla
Antonio Rodríguez-Moreno: Universidad Pablo de Olavide

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Presynaptic 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.

Date: 2020
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DOI: 10.1038/s41467-020-18024-4

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