Neocortical long-range inhibition promotes cortical synchrony and sleep
19 affiliations
- 1Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA
- 2UCL Queen Square Institute of Neurology, University College London, London, UK
- 3Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA. [email protected]
- 4Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected]
- 5Allen Institute for Brain Science, Seattle, WA, USA
- 6Department of Bioengineering, Stanford University, Stanford, CA, USA
- 7Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- 8Department of Neuroscience, University of Texas at Austin, Austin, TX, USA
- 9Department of Psychiatry and Behavioral Sciences, University of Texas at Austin, Austin, TX, USA
- 10Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA, USA
- 11Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
- 12Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA
- 13National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
- 14Biosciences Division, SRI International, Menlo Park, CA, USA
- 15Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, New York, NY, USA
- 16Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA. [email protected]
- 17Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, New York, NY, USA. [email protected]
- 18Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA. [email protected]
- 19Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected]
Abstract
Sleep and wakefulness are associated with distinct cortical patterns of rhythmic activity. 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 players of cortical state, the in vivo circuit mechanisms coordinating synchronized activity across local and distant neocortical networks remain poorly understood. Here, we show that somatostatin and chondrolectin co-expressing cells (Sst-Chodl), a sparse and genetically distinct class of neocortical GABAergic inhibitory neurons, are selectively active during low-arousal states and largely 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 via long-range axons that simultaneously target multiple regions. Selective activation of Sst-Chodl cells is sufficient to promote multi-region cortical synchronization characteristic of low-arousal states and to induce sleep. Together, these findings show that long-range Sst-Chodl inhibitory neurons not only track behavioral state but can actively promote sleep-like cortical activity and sleep behavior, highlighting an important contribution of cortical circuits to sleep regulation alongside established subcortical mechanisms.
Related
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- Cell type specific astrocytic feedback regulates excitation inhibition balance and cortical network dynamics
BibTeX
@article{ratliff2026neocortical,
title = {{Neocortical long-range inhibition promotes cortical synchrony and sleep}},
author = {Jacob M Ratliff and Geoffrey Terral and Arenski Vazquez and Stefano Lutzu and Arena Manning and Nelson A. Perez-Catalan and Gabriela Neubert da Silva and Soyoun Kim and Julie Mota and Matthew Mallory and Bianca Stith and Charu Ramakrishnan and Gianna Mattessich and Lief E. Fenno and Tanya L. Daigle and David A. Stafford and Hongkui Zeng and Bosiljka Tasic and Staci A. Sorensen and Karl A. Deisseroth and John Ngai and Thomas S. Kilduff and Lucas Sjulson and Stephanie Rudolph and Renata Batista‐Brito},
journal = {Nature},
year = {2026},
month = sep,
doi = {10.1038/s41586-026-10876-y},
url = {https://doi.org/10.1038/s41586-026-10876-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Neocortical long-range inhibition promotes cortical synchrony and sleep
AU - Jacob M Ratliff
AU - Geoffrey Terral
AU - Arenski Vazquez
AU - Stefano Lutzu
AU - Arena Manning
AU - Nelson A. Perez-Catalan
AU - Gabriela Neubert da Silva
AU - Soyoun Kim
AU - Julie Mota
AU - Matthew Mallory
AU - Bianca Stith
AU - Charu Ramakrishnan
AU - Gianna Mattessich
AU - Lief E. Fenno
AU - Tanya L. Daigle
AU - David A. Stafford
AU - Hongkui Zeng
AU - Bosiljka Tasic
AU - Staci A. Sorensen
AU - Karl A. Deisseroth
AU - John Ngai
AU - Thomas S. Kilduff
AU - Lucas Sjulson
AU - Stephanie Rudolph
AU - Renata Batista‐Brito
PY - 2026
DA - 2026/09/09
JO - Nature
DO - 10.1038/s41586-026-10876-y
UR - https://doi.org/10.1038/s41586-026-10876-y
AB - Sleep and wakefulness are associated with distinct cortical patterns of rhythmic activity. 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 players of cortical state, the in vivo circuit mechanisms coordinating synchronized activity across local and distant neocortical networks remain poorly understood. Here, we show that somatostatin and chondrolectin co-expressing cells (Sst-Chodl), a sparse and genetically distinct class of neocortical GABAergic inhibitory neurons, are selectively active during low-arousal states and largely 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 via long-range axons that simultaneously target multiple regions. Selective activation of Sst-Chodl cells is sufficient to promote multi-region cortical synchronization characteristic of low-arousal states and to induce sleep. Together, these findings show that long-range Sst-Chodl inhibitory neurons not only track behavioral state but can actively promote sleep-like cortical activity and sleep behavior, highlighting an important contribution of cortical circuits to sleep regulation alongside established subcortical mechanisms.
SN - 0028-0836
SN - 1476-4687
ER -