Falcón-Moya, R., Pérez-Rodríguez, M., Prius-Mengual, J., Andrade-Talavera, Y., Arroyo-García, L. E., Pérez-Artés, R., ... & Rodríguez-Moreno, A. (2020). Astrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development. Nature communications, 11(1), 1-14. DOI: 10.1038/s41467-020-18024-4
Nature Communications Portada


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, Antonio Rodríguez-Moreno


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


En este trabajo se ha descubierto que, durante el desarrollo postnatal, en el hipocampo, algunas de las formas de plasticidad que presenta (una depresión de larga duración, LTD) desaparece y de convierte en otra forma distinta de plasticidad (una potenciación de larga duración, LTP) conforme los animales (ratones) se van haciendo adultos y se han caracterizado en profundidad los mecanismos celulares y moleculares en los que los astrocitos desempeñan un papel central liberando glutamato y adenosina, revelando una nueva forma de LTP presináptica y las reglas para su inducción.

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El Laboratorio de Neurociencia Celular y Plasticidad de la Universidad Pablo de Olavide, de Sevilla está dedicado al estudio de los mecanismos celulares y moleculares que subyacen a los procesos de plasticidad neuronal y sus cambios durante es desarrollo postnatal. Así mismo, estudia la fisiología de los receptores de glutamato, particularmente los del tipo NMDA y kainato y su papel en la regulación de la liberación de glutamato, la inducción y mantenimiento de fenómenos de plasticidad y como posibles dianas terapéuticas en la recuperación de trastornos neurológicos.

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