Chávez, AndrésAndrésChávezFuenzalida, MarcoMarcoFuenzalidaNegrón, SergioSergioNegrónSotomayor, RamónRamónSotomayorFranco DíazF.T. Arruebo AguilarMario WellmannAndrés MartorellCamila González‐ArancibiaLorena Chacana-VélizIgnacio Negrón-OyarzoFrancisco NualartChristian Bonansco2025-08-252025-08-252023-09-2510.3390/ijms2419145062-s2.0-85174692295https://cris-uv-2.scimago.es/handle/123456789/4681WOS:001085637100001Epilepsy is a chronic condition characterized by recurrent spontaneous seizures. The interaction between astrocytes and neurons has been suggested to play a role in the abnormal neuronal activity observed in epilepsy. However, the exact way astrocytes influence neuronal activity in the epileptogenic brain remains unclear. Here, using the PTZ-induced kindling mouse model, we evaluated the interaction between astrocyte and synaptic function by measuring astrocytic Ca2+ activity, neuronal excitability, and the excitatory/inhibitory balance in the hippocampus. Compared to control mice, hippocampal slices from PTZ-kindled mice displayed an increase in glial fibrillary acidic protein (GFAP) levels and an abnormal pattern of intracellular Ca2+-oscillations, characterized by an increased frequency of prolonged spontaneous transients. PTZ-kindled hippocampal slices also showed an increase in the E/I ratio towards excitation, likely resulting from an augmented release probability of excitatory inputs without affecting inhibitory synapses. Notably, the alterations in the release probability seen in PTZ-kindled slices can be recovered by reducing astrocyte hyperactivity with the reversible toxin fluorocitrate. This suggests that astroglial hyper-reactivity enhances excitatory synaptic transmission, thereby impacting the E/I balance in the hippocampus. Altogether, our findings support the notion that abnormal astrocyte–neuron interactions are pivotal mechanisms in epileptogenesis.enacceso abiertoBiochemistry And Molecular BiologyChemistry, MultidisciplinaryCatalysisComputer Science ApplicationsInorganic ChemistryMedicineMolecular BiologyOrganic ChemistryPhysical And Theoretical ChemistrySpectroscopyarticle