Boccalaro Ida Luisa, Aime Mattia, Aellen Florence Marcelle, Rusterholz Thomas, Borsa Micaela, Bozic Ivan, Sattin Andrea, Fellin Tommaso, Herrera Carolina Gutierrez, Tzovara Athina, Adamantidis Antoine
Zentrum für Experimentelle Neurologie, Department of Neurology, Inselspital University Hospital Bern, University of Bern, Bern, Switzerland.
Department of Biomedical Research, University of Bern, Bern, Switzerland.
Nat Commun. 2025 Jul 31;16(1):7049. doi: 10.1038/s41467-025-62265-0.
Sleep involves a relative disconnection from the environment, yet sensory stimuli can still trigger awakenings. The mechanism underlying sensory vigilance and stimulus discrimination during sleep remains unclear. Here, we showed that neutral auditory stimuli evoked responses across parallel auditory and non-auditory pathways, including the auditory cortex and thalamus, the hippocampus and centro-medial thalamus (CMT). Using a convolutional neural network, we identified CMT activity as the most discriminant hub for auditory-evoked sleep-to-wake transitions among all recorded structures. Furthermore, we found that prior associative learning of auditory cues with danger (conditioned stimulus, CS+) resulted in increased awakening upon CS+ exposure during NREM, but not REM, sleep. These sleep-to-wake transitions were blocked by optogenetic silencing of CMT neurons during CS+ exposure in sleeping mice. Altogether, these results suggest a central role of the CMT neurons in the residual processing of behaviorally-relevant information in the sleeping brain functioning as one of the major hubs for awakening in response to danger.
睡眠涉及与环境的相对脱离，但感觉刺激仍可引发觉醒。睡眠期间感觉警觉和刺激辨别背后的机制尚不清楚。在这里，我们表明中性听觉刺激会在平行的听觉和非听觉通路中引发反应，包括听觉皮层和丘脑、海马体和中央内侧丘脑（CMT）。使用卷积神经网络，我们将CMT活动确定为所有记录结构中听觉诱发睡眠至觉醒转换的最具判别性的枢纽。此外，我们发现先前将听觉线索与危险（条件刺激，CS+）进行的联想学习导致在非快速眼动（NREM）睡眠而非快速眼动（REM）睡眠期间接触CS+时觉醒增加。在睡眠小鼠接触CS+期间，通过对CMT神经元进行光遗传学沉默，这些睡眠至觉醒的转换被阻断。总之，这些结果表明CMT神经元在睡眠大脑中行为相关信息的残余处理中起着核心作用，作为对危险做出反应的主要觉醒枢纽之一。
