Orexin- and MCH-Neurons Double-Ablated Mice Display Severe Sleep Attacks and Cataplexy

Orexin-producing neurons (orexin neurons) and melanin-concentrating hormone-producing neurons (MCH neurons) are exclusively distributed in the lateral hypothalamus and project throughout the whole brain to regulate sleep/wakefulness. Ablation of orexin neurons in mice decreases wakefulness in the dark period and they display a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. It is unclear how interaction between orexin and MCH neurons regulates sleep/wakefulness. Here we generated transgenic mice in which both orexin and MCH neurons are ablated. These double-ablated mice show increased wakefulness and decreased rapid eye movement (REM) and non-REM sleep. Total time and duration of cataplexy were significantly increased in double-ablated mice compared with orexin neurons-ablated mice. These results suggest that MCH neurons have a suppressive role in cataplexy. Interestingly, these mice showed frequent sleep attacks with high delta and theta wave power via electroencephalograms during wakefulness, which is not classified under conventional criteria of sleep/wakefulness or cataplexy.