한빛사논문
Hanna Antila 1, Iris Kwak 1, Ashley Choi 1, Alexa Pisciotti 1, Ivan Covarrubias 1, Justin Baik 1, Amelia Eisch 1 2, Kevin Beier 3, Steven Thomas 4, Franz Weber 1, Shinjae Chung 1
1Department of Neuroscience, Chronobiology, and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
2Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104.
3Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92617.
4Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
To whom correspondence may be addressed. : Shinjae Chung
Abstract
In our daily life, we are exposed to uncontrollable and stressful events that disrupt our sleep. However, the underlying neural mechanisms deteriorating the quality of non-rapid eye movement sleep (NREMs) and REM sleep are largely unknown. Here, we show in mice that acute psychosocial stress disrupts sleep by increasing brief arousals (microarousals [MAs]), reducing sleep spindles, and impairing infraslow oscillations in the spindle band of the electroencephalogram during NREMs, while reducing REMs. This poor sleep quality was reflected in an increased number of calcium transients in the activity of noradrenergic (NE) neurons in the locus coeruleus (LC) during NREMs. Opto- and chemogenetic LC-NE activation in naïve mice is sufficient to change the sleep microarchitecture similar to stress. Conversely, chemogenetically inhibiting LC-NE neurons reduced MAs during NREMs and normalized their number after stress. Specifically inhibiting LC-NE neurons projecting to the preoptic area of the hypothalamus (POA) decreased MAs and enhanced spindles and REMs after stress. Optrode recordings revealed that stimulating LC-NE fibers in the POA indeed suppressed the spiking activity of POA neurons that are activated during sleep spindles and REMs and inactivated during MAs. Our findings reveal that changes in the dynamics of the stress-regulatory LC-NE neurons during sleep negatively affect sleep quality, partially through their interaction with the POA.
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