not-yet-known not-yet-known not-yet-known unknown Human tissue samples Human tissue samples were used at the Lisbon and Rome institutions. Samples were provided by the Department of NeuroPathology of the Amsterdam University Medical Center and by Biobank from Instituto de Medicina Molecular João Lobo Antunes (iMM). The use of human samples was approved by the Ethics Committee from Centro Hospitalar Universitário Lisboa Norte and Centro Académico de Medicina de Lisboa (nº 207/21) and met the Portuguese Law on Clinical Research (Lei n. º 21/2014, de 16 de abril), amended in law (Lei n. º 73/2015, de 27 de Julho), as well as approved by the Ethics and Biobank Committees of the Amsterdam UMC and University of Rome. The iMM Biobank provided frozen samples of the hippocampus from 11 patients submitted to temporal lobe resections due to refractory epilepsy, after an extensive presurgical evaluation at “Centro de Referência para a área da epilepsia refratária” (Centro Hospitalar Lisboa Norte), member of the ERN EpiCARE for Complex and rare epilepsies, and under informed consent. These samples were used for Western blot analysis shown in Figure 6; additional information on these samples can be found in Table 2. Human tissue samples for recordings of GABAergic currents were selected from the Department of Neuropathology of the Academic Medical Center (AMC, University of Amsterdam) and the VU University Medical Center (VUMC) and sent frozen to Sapienza University of Rome. The AMC Research code was provided by the Medical Ethics Committee. GABAergic current recordings were performed using a total of 3 surgical epilepsy specimens (hippocampus) from patients that underwent surgery for refractory temporal lobe epilepsy (TLE). In the text, the number of patients used in each experiment is referred with the symbol # (additional information can be found in Table 3). A presurgical evaluation conducted with non-invasive tests was carried out in all patients, and patients were excluded from the study in cases where implantation of strip and/or grid electrodes for chronic subdural invasive monitoring before resection was necessary. All surgeries were performed at VUMC. The predominant seizure types were medically intractable, focal impaired awareness seizures, and all patients were resistant to maximal doses of different anti-epileptic drugs. No patients included in our series had seizures in the 24 hours before surgery. All cases were reviewed independently by two neuropathologists, and the diagnosis was confirmed according to the international consensus classification (Blümcke et al., 2013). As control tissues for both GABAergic current recordings (data in Figure 7, details in Table 3, # 4) and for Western Blot analysis (data in Figure 6, details in Table 2), we used brain samples from autopsies of individuals with no neurological disorders and no history of neurological disease or signs of neuroinflammation, which were also selected and provided by Department of NeuroPathology of the Amsterdam University Medical Center. In all cases, tissue was obtained and used in accordance with the Declaration of Helsinki, as well as the Amsterdam UMC research code and protocol approved by the local (Lisbon and Rome) Biobank Research Ethics Committee. The samples were maintained at -80 °C until further processing.