Neocortical long-range inhibition promotes cortical synchrony and sleep
- 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
2026-09-09
Sleep and wakefulness are associated with distinct cortical patterns of rhythmic activity 1 . 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 state 2–4 , 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.