Neocortical long-range inhibition promotes cortical synchrony and sleep.

Authors

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

Published in

Nature. Sep 09, 2026. Epub Sep 09, 2026.

Abstract

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 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.

PMID:
42717094
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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