c-Maf Deletion in Cortical Somatostatin, But Not Parvalbumin, Interneurons Leads to Absence-Like Epileptiform Activity in Mice.

Mafb and c-Maf transcription factors (TFs) are expressed in medial ganglionic eminence (MGE) lineages, beginning in progenitors and continuing into mature GABAergic parvalbumin-positive (PV+) and somatostatin-positive (SST+) cortical interneurons (CINs). Deleting Mafb and c-Maf in MGE before SST versus PV fate specification causes developmental anomalies, including altered numbers of CINs and seizure phenotypes, but the specific contributions of these TFs in postmitotic SST+ and PV+ CINs to epilepsy remain unknown. To address this, we conditionally deleted Mafb or c-Maf in SST+ or PV+ interneurons after interneuron fate specification in female and male mice. Deletion of c-Maf, but not Mafb, in SST+ cells was associated with reduced synaptic excitation onto these cells and with spontaneous spike-and-wave discharges, consistent with absence-like seizures. In contrast, deletion of Mafb in SST+ CINs reduced their density in superficial cortical layers but did not induce epilepsy. Neither c-Maf nor Mafb deletion in PV+ CINs produced major electrophysiological or histological abnormalities in the somatosensory cortex. These findings identify a specific requirement for c-Maf in modulating synaptic excitation of SST+ interneurons and show that its loss in SST+ cells is associated with the development of absence-like epileptiform activity in vivo. Together, our results refine the understanding of how transcriptional programs shape interneuron function in the mature cortex and highlight c-Maf/MAF-dependent pathways as candidates for investigation in epilepsy genetics.