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Sodium channels add variety to inhibitory interneurons Different populations of inhibitory interneurons in the cerebral cortex express distinct subtypes of sodium channels, resulting in diverse action potential thresholds and network excitability., Action potential (AP) generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV)- and somatostatin (SST)-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV) than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS) of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity., Author Summary Inhibitory interneurons in the cerebral cortex are diverse in many respects. Here, we examine whether this diversity extends to the composition of ion channels along the axon, which might determine the neurons' excitability. We performed patch-clamp recordings from cortical interneuron axons in brain slices obtained from two transgenic mouse lines. In each mouse line, distinct populations of inhibitory interneurons—those that express parvalbumin (PV) or those that express somatostatin (SST)—were labeled with green fluorescent protein to allow visualization. We show that action potentials initiate at the axon initial segment (a specialized region of the axon closest to the cell body) in both cell types, but SST neurons have a higher action potential threshold than PV neurons because their sodium channels require a greater degree of depolarization to be fully activated. At the molecular level, we found that the population of sodium channels in SST neurons requires a larger depolarization because it has a more mixed composition of high- and low-threshold sodium channel subtypes. In summary, this study reveals diversity in the molecular identity and voltage dependence of sodium channels that are responsible for initiating action potentials in different populations of interneurons. In addition, the presence of a particular subtype of sodium channel—NaV1.2—in inhibitory interneurons might explain why loss-of-function mutations in this channel result in epilepsy.