Somatostatin neurons in prefrontal cortex initiate sleep-preparatory behavior and sleep via the preoptic and lateral hypothalamus

  • Nat Neurosci. 2023 Oct;26(10):1805-1819. doi: 10.1038/s41593-023-01430-4.
Kyoko Tossell  #  1 ,  Xiao Yu  #  1  2 ,  Panagiotis Giannos  1 ,  Berta Anuncibay Soto  1  3 ,  Mathieu Nollet  1  3 ,  Raquel Yustos  1 ,  Giulia Miracca  1 ,  Mikal Vicente  1 ,  Andawei Miao  1  3 ,  Bryan Hsieh  1  4  5 ,  Ying Ma  1 ,  Alexei L Vyssotski  6 ,  Tim Constandinou  4  5  7 ,  Nicholas P Franks  8  9  10 ,  William Wisden  11  12  13
Affiliations
  • 1. Department of Life Sciences, Imperial College London, London, UK.
  • 2. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
  • 3. UK Dementia Research Institute, Imperial College London, London, UK.
  • 4. Department of Electrical and Electronic Engineering, Imperial College London, London, UK.
  • 5. Center for Neurotechnology, Imperial College London, London, UK.
  • 6. Institute of Neuroinformatics, University of Zürich-ETH Zürich, Zürich, Switzerland.
  • 7. Care Research and Technology Centre, UK Dementia Research Institute, London, UK.
  • 8. Department of Life Sciences, Imperial College London, London, UK. [email protected].
  • 9. UK Dementia Research Institute, Imperial College London, London, UK. [email protected].
  • 10. Center for Neurotechnology, Imperial College London, London, UK. [email protected].
  • 11. Department of Life Sciences, Imperial College London, London, UK. [email protected].
  • 12. UK Dementia Research Institute, Imperial College London, London, UK. [email protected].
  • 13. Center for Neurotechnology, Imperial College London, London, UK. [email protected].
  • # Contributed equally.
PMID: 37735497 DOI: 10.1038/s41593-023-01430-4
Abstract

The prefrontal cortex (PFC) enables mammals to respond to situations, including internal states, with appropriate actions. One such internal state could be 'tiredness'. Here, using activity tagging in the mouse PFC, we identified particularly excitable, fast-spiking, somatostatin-expressing, γ-aminobutyric acid (GABA) (PFCSst-GABA) cells that responded to sleep deprivation. These cells projected to the lateral preoptic (LPO) hypothalamus and the lateral hypothalamus (LH). Stimulating PFCSst-GABA terminals in the LPO hypothalamus caused sleep-preparatory behavior (nesting, elevated theta power and elevated temperature), and stimulating PFCSst-GABA terminals in the LH mimicked recovery sleep (non-rapid eye-movement sleep with higher delta power and lower body temperature). PFCSst-GABA terminals had enhanced activity during nesting and sleep, inducing inhibitory postsynaptic currents on diverse cells in the LPO hypothalamus and the LH. The PFC also might feature in deciding sleep location in the absence of excessive fatigue. These findings suggest that the PFC instructs the hypothalamus to ensure that optimal sleep takes place in a suitable place.