Lee Sang Soo, Liu Qiang, Cheng Alexandra H R, Kim Dong Won, Boudreau Daphne M, Mehta Anuradha, Keles Mehmet F, Fejfer Rafal, Palmer Isabelle, Park Kristen H, Münzberg Heike, Harris Timothy D, Graves Austin R, Blackshaw Seth, Wu Mark N
Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Science. 2025 Jun 19;388(6753):eadm8203. doi: 10.1126/science.adm8203.
Prolonged wakefulness leads to persistent, deep recovery sleep (RS). However, the neuronal circuits that mediate this process remain elusive. From a circuit screen in mice, we identified a group of thalamic nucleus reuniens (RE) neurons activated during sleep deprivation (SD) and required for sleep homeostasis. Optogenetic activation of RE neurons leads to an unusual phenotype: presleep behaviors (grooming and nest organizing) followed by prolonged, intense sleep that resembles RS. Inhibiting RE activity during SD impairs subsequent RS, which suggests that these neurons signal sleep need. RE neurons act upstream of sleep-promoting zona incerta cells, and SD triggers plasticity of this circuit to strengthen their connectivity. These findings reveal a circuit mechanism by which sleep need transforms the functional coupling of a sleep circuit to promote persistent, deep sleep.
长时间清醒会导致持续的深度恢复性睡眠（RS）。然而，介导这一过程的神经回路仍然难以捉摸。通过对小鼠的回路筛选，我们鉴定出一组在睡眠剥夺（SD）期间被激活且对睡眠稳态至关重要的丘脑 reunens 核（RE）神经元。RE 神经元的光遗传学激活会导致一种不寻常的表型：睡眠前行为（梳理毛发和整理巢穴），随后是类似于 RS 的长时间深度睡眠。在 SD 期间抑制 RE 活动会损害随后的 RS，这表明这些神经元传递睡眠需求信号。RE 神经元在促进睡眠的未定带细胞上游起作用，并且 SD 触发该回路的可塑性以增强它们的连接性。这些发现揭示了一种回路机制，通过该机制睡眠需求改变睡眠回路的功能耦合以促进持续的深度睡眠。
