Ventrolateral periaqueductal gray mediates rapid eye movement sleep regulation by melanin-concentrating hormone neurons

Abstract Neurons containing melanin-concentrating hormone (MCH) in the lateral hypothalamic area (LH) have been shown to promote rapid eye movement sleep (REMs) in mice. However, the downstream neural pathways through which MCH neurons influence REMs remained unclear. Because MCH neurons are considered to be primarily inhibitory, we hypothesized that these neurons inhibit the midbrain ‘REMs-suppressing’ region consisting of the ventrolateral periaqueductal gray and the lateral pontine tegmentum (vlPAG/LPT) to promote REMs. To test this hypothesis, we optogenetically inhibited MCH terminals in the vlPAG/LPT under baseline conditions as well as with simultaneous chemogenetic activation of MCH soma. We found that inhibition of MCH terminals in the vlPAG/LPT significantly reduced transitions into REMs during spontaneous sleep–wake cycles and prevented the increase in REMs transitions observed after chemogenetic activation of MCH neurons. These results strongly suggest that the vlPAG/LPT may be an essential relay through which MCH neurons modulate REMs.