Dexmedetomidine promotes NREM sleep by depressing the neuronal activity of OXT neurons in the PVN

This study aimed to investigate the mechanism of Dexmedetomidine (DEX) on sleep homeostasis. We will focus on the effect of DEX on the activity and the signal transmission of oxytocin-expressing (Oxytocin, OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVN^OXT) in the regulation of sleep-wakefulness cycle. In this study, the guide cannula was implanted to microinject DEX into PVN. PVN^OXT neurons were specifically activated by the chemogenetic method. Differences in sleep-wakefulness states were monitored by electroencephalogram (EEG)/ electromyogram (EMG) recording. In addition, the effect of DEX on the electrophysiological activity of PVN^OXT neurons was examined by whole-cell patch-clamp technique. EEG/EMG results showed that microinjection of DEX in PVN significantly increased the duration of nonrapid eye movement (NREM) sleep in mice. Chemogenetic activation of PVN^OXT neurons after internal cannula injection of DEX to PVN increased the amount of wake. Electrophysiological results show that DEX could inhibit the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) in PVN^OXT neurons through α₂-adrenoceptors. DEX maintained sleep homeostasis by inhibiting excitatory synaptic signaling in PVN^OXT neurons through α₂-adrenoceptors.