| Popis: |
The noradrenergiclocus coeruleus(LC) supports vital brain functions during wakefulness. In contrast, the LC has been associated with sleep-promotion and -disruption, leaving its functions for sleep uncertain. Here, we show that the LC is essential for the progression of natural, undisturbed sleep because it creates a non-reducible timeframe for the non-rapid-eye-movement (NREM) sleep-REM sleep cycle. Fiber-photometric jGCaMP8s-based LC activity measures, closed-loop optogenetics and mouse sleep-wake monitoring revealed that LC showed ∼50-s-activity fluctuations, during which high activity levels promoted a NREMS with high arousability, while low levels a NREMS with the opportunity for transitions to REMS. The NREMS-REMS cycle was shortened by LC inhibition due to precocious REMS onset. Supporting LC’s pivotal role as a gatekeeper of the NREMS-REMS cycle, REMS entries occurred on intervals no shorter than ∼50 s during REMS-restriction. A stimulus- enriched wake experience strengthened LC fluctuations, which contributed to subsequent NREMS fragmentation and delayed REMS. The LC fluctuations are hence indispensable for the NREMS-REMS cycle but they can become sleep-disruptive as a result of prior wake experience. |
