冬天总是睡不醒？多篇高分文献揭示睡眠开关在哪里

Neural control of rapid adenosine dynamics and sleep homeostasis. (A) Simultaneous optical recording of the Ca2+ activity and adenosine concentration using GCaMP and GRABAdo reveals neural activity–dependent rapid adenosine dynamics in the mouse basal forebrain (BF) during the sleep-wake cycle. (B) Optogenetic activation of BF glutamatergic neurons evokes a robust increase of extracellular adenosine. (C) Cell type–specific lesion of BF glutamatergic neurons significantly increases wakefulness.

Fig. 1. Lower NE signaling decreases the probability of SEAs from NREM sleep. (A) Representative EEG and EMG traces showing immediate awakenings (top) versus maintained sleep (bottom) after auditory stimulation (4-kHz pure tone, 1-s duration; orange bars) in NREM sleep (left) and REM sleep (right). (B) Probability of awakenings (%) as a function of sound intensity in NREM sleep (purple) and REM sleep (dark blue). Gray circles show individual subject data (n = 4 rats). (C) Schematic of experimental setup for rat arousal threshold experiments (each lasting ~12 hours during lights on periods, with ~400 tone pips presented every 105 s on average). Sounds were delivered intermittently from speaker on top, while animals were continuously monitored with EEG, EMG, and video. In pharmacological experiments, NE drugs were injected intraperitoneally at lights on (10:00 a.m.). (D) Probability of awakenings (%) as a function of sound intensity in NREM sleep following administration of detomidine (α2 agonist, lower NE; green), yohimbine (α2 antagonist, higher NE; blue), or saline (gray). Note that lower NE decreases awakening probability. Two-way repeated-measures (RM) ANOVA, followed by post hoc t tests corrected with false discovery rate (FDR) *P < 0.05 and **P < 0.01 in n = 6 rats.

Fig.1 Population activity of VP GABAergic neurons across sleep–wake states. a Schematic of in vivo fiber photometry recordings. b Unilateral viral targeting of AAV-EF1α-DIO-GCaMP6f into the VP of a Vgat-Cre mouse. Right: Viral expression of GCaMP6f and the placement of the fiber-optic probe in the VP. Scale bar = 200 μm. c GFP-expressing cells were GABA-positive. Scale bar= 20 μm (n= 4 mice). d Representative fluorescent traces, relative EEG power, and EEG/EMG traces across spontaneous sleep–wake states. e ΔF/F peaks during wakefulness, NREM sleep, and REM sleep. The fluorescent peak values were normalized by the mean ΔF/F peaks during NREM sleep (n = 4 mice, ten sessions per mouse, **P < 0.01, one-way ANOVA followed by Tukey’s post-hoc test). 

Fig. 1. Optogenetic stimulation of the CRF neurons in the PVN promotes wakefulness. (A) Schematic drawing of anterograde tracing experiment (top) and fluorescence image of the SCN in a GAD67-Cre mouse injected with AAV-CMV-flex-hrGFP (bottom). (B) Fluorescence images of several brain areas in a GAD67-Cre mouse with AAV-CMV-flex-hrGFP injected into the SCN. (C) Schematic drawing of optogenetic activation experiment in vivo and fluorescence image of the PVN in a CRF-Cre mouse injected with AAV-CMV-flex-ChR2-EYFP. (D) A fluorescence image of ChR2-EYFP (green), CRF (red), and DAPI (4′,6-diamidino-2-phenylindole) (blue) of the PVN in a CRFCre mouse. (E) A representative example of the electroencephalography (EEG) and electromyography (EMG) traces, together with the EEG power spectrum. The blue bar indicates light stimulation (10 Hz for 30 s). (F) Probability of wakefulness and NREM and REM sleep before, during, and after blue light stimulation (mean ± SD). Blue shading areas indicate light flashing. (G) Statistical results of the probability of a vigilant state before (indicated as “b”), during, and after blue light stimulation. The mean probability during 12 s (three epochs) obtained from (F) is shown in the bar graphs (mean ± SD; n = 5). Blue characters (1 to 3) indicate during stimulation (*P < 0.05 versus baseline; one-way repeated-measures analysis of variance with post hoc Tukey-Kramer test, or Friedman test with post hoc Steel-Dwass test). PVT, paraventricular thalamus; OVLT, organum vasculosum laminae terminalis; AVPV, anteroventral periventricular nucleus; VMH, ventromedial hypothalamus; D3V, dorsal part of the third ventricle.