Jacob M Ratliff, Geoffrey Terral, Arenski Vazquez, Stefano Lutzu, Arena Manning, Nelson Perez-Catalan, Gabriela Neubert da Silva, Soyoun Kim, Julie Mota, Matt Mallory, Bianca Stith, Charu Ramakrishnan, Gianna Mattessich, Lief E Fenno, Tanya Daigle, David A Stafford, Hongkui Zeng, Bosiljka Tasic, Staci Sorensen, Karl Deisseroth, John Ngai, Thomas S Kilduff, Lucas Sjulson, Stephanie Rudolph, Renata Batista-Brito
Sleep and wakefulness are associated with distinct cortical patterns of rhythmic activity1. During low-arousal states such as slow-wave sleep, synchronous low-frequency rhythms dominate activity across widespread cortical regions. Although inhibitory neurons are increasingly recognized as key regulators of cortical state2-4, the circuit mechanisms that coordinate synchronized activity across local and distant neocortical networks in vivo remain poorly understood. Here we show in mice that cells co-expressing somatostatin (Sst) and chondrolectin (Chodl)-which constitute a sparse and genetically distinct class of neocortical GABAergic inhibitory neurons-are selectively active during low-arousal states and mostly silent during periods of high arousal. In contrast to most neocortical inhibitory neurons, Sst-Chodl cells, despite being extremely sparse, exert widespread influence across the neocortex, through long-range axons that target multiple regions simultaneously. Selective activation of Sst-Chodl cells is sufficient to promote the multi-region cortical synchronization that is characteristic of low-arousal states and to induce sleep. Together, these findings show that long-range Sst-Chodl inhibitory neurons not only track behavioural state, but can also actively promote synchronized cortical activity and sleep behaviour, highlighting that cortical circuits have a key role in sleep regulation, alongside established subcortical mechanisms.