Chouvaeff Mathilde, Descamps Alice, Bagur Sophie, Macé Léo, Benchenane Karim, Gallopin Thierry
Brain Plasticity Unit, CNRS, ESPCI-Paris, PSL Research University, Paris 75005, France.
Brain Plasticity Unit, CNRS, ESPCI-Paris, PSL Research University, Paris 75005, France.
Curr Biol. 2025 Sep 8;35(17):4151-4164.e4. doi: 10.1016/j.cub.2025.07.039. Epub 2025 Aug 6.
The cerebral structures orchestrating the daily cycles of wake, rapid eye movement (REM), and non-rapid eye movement (NREM) sleep have been identified in remarkable detail. However, the mechanisms by which they dynamically adapt to environmental challenges remain to be fully understood. Here, we show that the prefrontal cortex (PFC), a key hub in stress regulation, modulates sleep architecture through direct projections to the ventrolateral preoptic nucleus (VLPO), a major sleep center. We characterize the detailed sleep architecture in mice after social defeat stress (SDS) and discover, for the first time, a persistent shortening of REM sleep bouts during the light phase, which outlasts the normalization of overall NREM sleep, REM sleep, and wakefulness proportions. This shift, marked by an increase in short REM sleep episodes and a reduction in long ones, is reminiscent of the fragmentation of REM sleep bouts often described in stress-related conditions. Chemogenetic inhibition of PFC to VLPO projections has no effect under baseline conditions but prevents the SDS-induced shortening of REM sleep bouts. Interestingly, optogenetic activation of this pathway is sufficient to shorten REM sleep episodes, despite the absence of the stressor, and promotes rapid transitions into NREM sleep. Finally, using ex vivo optogenetics, we demonstrate that activation of PFC terminals induces monosynaptic currents in VLPO sleep-promoting neurons. Therefore, the PFC-VLPO pathway provides top-down regulation specifically recruited under stress to shorten REM sleep episodes and increase transitions into NREM sleep while preserving total NREM sleep duration.
负责协调清醒、快速眼动（REM）和非快速眼动（NREM）睡眠日常周期的大脑结构已被详细识别。然而，它们如何动态适应环境挑战的机制仍有待充分了解。在这里，我们表明前额叶皮层（PFC）作为应激调节的关键枢纽，通过直接投射到主要睡眠中心腹外侧视前核（VLPO）来调节睡眠结构。我们对遭受社会挫败应激（SDS）后的小鼠详细睡眠结构进行了表征，并首次发现，在光照期REM睡眠时段持续缩短，这种情况在整体NREM睡眠、REM睡眠和清醒比例恢复正常后仍持续存在。这种变化以短REM睡眠发作增加和长REM睡眠发作减少为特征，让人联想到在与应激相关的情况下经常描述的REM睡眠时段碎片化。在基线条件下，对PFC到VLPO投射进行化学遗传学抑制没有效果，但可防止SDS诱导的REM睡眠时段缩短。有趣的是，尽管没有应激源，但该通路的光遗传学激活足以缩短REM睡眠发作，并促进快速过渡到NREM睡眠。最后，使用离体光遗传学，我们证明PFC终末的激活会在VLPO促进睡眠的神经元中诱导单突触电流。因此，PFC-VLPO通路提供自上而下的调节，在应激状态下被特别激活，以缩短REM睡眠发作并增加向NREM睡眠的过渡，同时保持总的NREM睡眠时间。
