Behavioral state and stimulus strength regulate the role of somatostatin interneurons in stabilizing network activity

Inhibition stabilization enables cortical circuits to encode sensory signals across diverse contexts. Somatostatin-expressing (SST) interneurons are well suited for this role through their strong recurrent connectivity with excitatory pyramidal cells. We tested the necessity of SST cells for inhibition stabilization in mouse primary visual cortex by selectively blocking excitatory glutamatergic receptors on SST cells. Antagonizing this key input for the recruitment of SST cells drives a paradoxical facilitation of their activity—the hallmark of inhibition stabilization—with increasing stimulus contrast, and even more so with high arousal. In a computational model of the visual cortex circuit, increasing sensory input and arousal both move the network toward a regime where other classes of interneurons are no longer sufficient for maintaining network stability. Thus, we reveal that the role of SST cells in cortical processing gradually switches as a function of both input strength and behavioral state.