Orexin and MCH neurons project throughout the brain ( Bittencourt et al., 1992 Peyron et al., 1998 Nambu et al., 1999) and are implicated in feeding and sleep/wakefulness ( Sakurai et al., 1998 Shimada et al., 1998 Chemelli et al., 1999 Verret et al., 2003). Orexin/hypocretin-(encoded by the Hcrt gene) and melanin-concentrating hormone (MCH, encoded by the Pmch gene)-producing neurons are distributed within the LH MCH neurons also extend caudally into the zona incerta. The lateral hypothalamus (LH) has long been known to be involved in the regulation of sleep/wakefulness, feeding behavior and metabolism ( Théodoridès and Vetter, 1972). 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. 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’. Double-ablated mice showed severe cataplexy compared with orexin neuron-ablated mice, suggesting that MCH neurons normally suppress cataplexy. Double-ablated mice exhibited increased wakefulness and decreased both rapid eye movement (REM) and non-REM (NREM) sleep. 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. Ablation of orexin neurons decreases wakefulness and results in a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. 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.

Mch neurons mouse brain