Article April 21, 2020
Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexySRI Authors Thomas Kilduff
Hung CJ, Ono D, Kilduff TS, and Yamanaka A. Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy. eLife 9:e54275.
Orexin/hypocretin-producing and melanin-concentrating hormone-producing (MCH) neurons are co-extensive in the hypothalamus and project throughout the brain to regulate sleep/wakefulness. Ablation of orexin neurons decreases wakefulness and results in a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. Since it is unclear how orexin and MCH neurons interact to regulate sleep/wakefulness, we generated transgenic mice in which both orexin and MCH neurons could be ablated. Double-ablated mice exhibited increased wakefulness and decreased both rapid eye movement (REM) and non-REM (NREM) sleep. Double-ablated mice showed severe cataplexy compared with orexin neuron-ablated mice, suggesting that MCH neurons normally suppress cataplexy. Double-ablated mice also showed frequent sleep attacks with elevated spectral power in the delta and theta range, a unique state that we call ‘delta-theta sleep’. Together, these results indicate a functional interaction between orexin and MCH neurons in vivo that suggests the synergistic involvement of these neuronal populations in the sleep/wakefulness cycle.
Figure 1—figure supplement 1.. In situ RNA hybridization of orexin, MCH, vGlut2 and vGAT: orexin- and MCH-positive cells were colocalized with vGlut2 but not with vGAT.
Figure 4.. DOX removal from the diet in OXMC mice does not affect relative EEG power distribution or the EMG integral.