4.8 Article

The subthalamic corticotropin-releasing hormone neurons mediate adaptive REM-sleep responses to threat

Journal

NEURON
Volume 110, Issue 7, Pages 1223-+

Publisher

CELL PRESS
DOI: 10.1016/j.neuron.2021.12.033

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Funding

  1. National Natural Science Foundation of China [31930047, 31630031]
  2. Key-Area Research and Development Program of Guangdong Province [2018B030331001]
  3. CAS Key Laboratory of Brain Connectome and Manipulation [2019DP173024]
  4. International Partnership Program of Chinese Academy of Sciences [172644KYS820170004]
  5. Strategic Priority Research Program of the Chinese Academy of Sciences [XDB32030103]
  6. Chinese Academy of Sciences Taiwan Young Talent Programme [2018TW2GB0002]
  7. Scientific Instrument Developing Project of the Chinese Academy of Sciences [YJKYYQ20170064]

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This study found that animals are rapidly aroused from REM sleep when facing threats, in contrast to NREM sleep. Neurons in the medial subthalamic nucleus expressing corticotropin-releasing hormone were identified as being responsible for mediating arousal and defensive responses to predator threats during sleep and wakefulness. These findings suggest that REM sleep responses are adaptive and may have a protective function against threats.
When an animal faces a threatening situation while asleep, rapid arousal is the essential prerequisite for an adequate response. Here, we find that predator stimuli induce immediate arousal from REM sleep compared with NREM sleep. Using in vivo neural activity recording and cell-type-specific manipulations, we identify neurons in the medial subthalamic nucleus (mSTN) expressing corticotropin-releasing hormone (CRH) that mediate arousal and defensive responses to acute predator threats received through multiple sensory modalities across REM sleep and wakefulness. We observe involvement of the same neurons in the normal regulation of REM sleep and the adaptive increase in REM sleep induced by sustained predator stress. Projections to the lateral globus pallidus (LGP) are the effector pathway for the threat-coping responses and REM-sleep expression. Together, our findings suggest adaptive REM-sleep responses could be protective against threats and uncover a critical component of the neural circuitry at their basis.

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