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Severe myoclonic epilepsy of infancy (SMEI) is associated with loss of function of theSCN1Agene encoding the NaV1.1 sodium channel isoform. Previous studies inScn1a−/+ mice during the pre-epileptic period reported selective reduction in interneuron excitability and proposed this as the main pathological mechanism underlying SMEI. Yet, the functional consequences of this interneuronal dysfunction at the circuit level in vivo are unknown. Here, we investigated whetherScn1a−/+ mice showed alterations in cortical network function. We found that various forms of spontaneous network activity were similar inScn1a−/+ during the pre-epileptic period compared with wild-type (WT) in vivo. Importantly, in brain slices fromScn1a−/+ mice, the excitability of parvalbumin (PV) and somatostatin (SST) interneurons was reduced, epileptiform activity propagated more rapidly, and complex synaptic changes were observed. However, in vivo, optogenetic reduction of firing in PV or SST cells in WT mice modified ongoing network activities, and juxtasomal recordings from identified PV and SST interneurons showed unaffected interneuronal firing during spontaneous cortical dynamics inScn1a−/+ compared with WT. These results demonstrate that interneuronal hypoexcitability is not observed inScn1a−/+ mice during spontaneous activities in vivo and suggest that additional mechanisms may contribute to homeostatic rearrangements and the pathogenesis of SMEI.