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Article
Xia Zhang
University of Ottawa
Corresponding Author
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Cannabinoids promote non-rapid eye movement (NREM) sleep, but its underlying mechanism is not known. Here we find that cannabinoid promotion of NREM sleep is inhibited by cannabinoid antagonist injection systemically or into the dorsomedial hypothalamus (DMH), where cannabinoids selectively inhibit glutamatergic inputs synapsing with glutamatergic but not GABAergic neurons. Photoactivation of DMH-projecting ventromedial prefrontal cortical (vmPFC) neurons, their terminals, or their postsynaptic DMH neurons rapidly switches NREM sleep to wakefulness, which is blocked by photoinhibition of DMH outputs. Chemoactivation of DMH glutamatergic but not GABAergic neurons innervated by vmPFCs promotes wakefulness and suppresses NREM sleep, whereas chemoinhibition of vmPFC projections in DMHs produces opposite effects by mimicking cannabinoid effects. DMH-projecting vmPFC neurons are inhibited during NREM sleep and activated during wakefulness. Chemoactivation of DMH-projecting vmPFC neurons blocks cannabinoid promotion of NREM sleep and suppression of wakefulness. Thus, vmPFC neurons innervating DMHs represent the first identified set of cerebral cortical neurons for promotion of physiological wakefulness and suppression of NREM sleep, while cannabinoid inhibition of vmPFC projections in DMHs promotes NREM sleep and suppresses wakefulness.
Keywords
Cannabinoid Antagonist Injection, Dorsomedial Hypothalamus, Glutametergic Inputs, Ventromedial Prefrontal Cortical Neurons, Physiological Wakefulness
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There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- 31Video1Normal.mp4
Video 1
- 32Video2REM.mp4
Video 2
- 33Video4Double.mp4
Video 3
- 34Video3WtoS.mp4
Video 4
- FiguresS1S10.pdf
Supplementary Figures
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Article
Xia Zhang
University of Ottawa
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 16 Nov, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular & Molecular Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Cannabinoids promote non-rapid eye movement (NREM) sleep, but its underlying mechanism is not known. Here we find that cannabinoid promotion of NREM sleep is inhibited by cannabinoid antagonist injection systemically or into the dorsomedial hypothalamus (DMH), where cannabinoids selectively inhibit glutamatergic inputs synapsing with glutamatergic but not GABAergic neurons. Photoactivation of DMH-projecting ventromedial prefrontal cortical (vmPFC) neurons, their terminals, or their postsynaptic DMH neurons rapidly switches NREM sleep to wakefulness, which is blocked by photoinhibition of DMH outputs. Chemoactivation of DMH glutamatergic but not GABAergic neurons innervated by vmPFCs promotes wakefulness and suppresses NREM sleep, whereas chemoinhibition of vmPFC projections in DMHs produces opposite effects by mimicking cannabinoid effects. DMH-projecting vmPFC neurons are inhibited during NREM sleep and activated during wakefulness. Chemoactivation of DMH-projecting vmPFC neurons blocks cannabinoid promotion of NREM sleep and suppression of wakefulness. Thus, vmPFC neurons innervating DMHs represent the first identified set of cerebral cortical neurons for promotion of physiological wakefulness and suppression of NREM sleep, while cannabinoid inhibition of vmPFC projections in DMHs promotes NREM sleep and suppresses wakefulness.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- 31Video1Normal.mp4
Video 1
- 32Video2REM.mp4
Video 2
- 33Video4Double.mp4
Video 3
- 34Video3WtoS.mp4
Video 4
- FiguresS1S10.pdf
Supplementary Figures
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