MCHergic projections to the nucleus pontis oralis participate in the control of active (REM) sleep

Neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator are located in the lateral hypothalamus and incerto-hypothalamic area and project diffusely throughout the central nervous system, including areas that participate in the generation and maintenance of sleep and wakefulness. Recent studies have shown that hypothalamic MCHergic neurons are active during active sleep (AS), and that intraventricular microinjections of MCH induce AS sleep; however, there are no data available regarding the manner in which MCHergic neurons participate in the control of this behavioral state.Utilizing immunohistochemical and retrograde tracing techniques, we examined, in the cat, projections from MCHergic neurons to the nucleus pontis oralis (NPO), which is considered to be the executive area that is responsible for the generation and maintenance of AS. In addition, we explored the effects on sleep and waking states produced by the microinjection of MCH into the NPO. We first determined that MCHergic fibers and terminals are present in the NPO. We also found that when a retrograde tracer (cholera toxin subunit B) was placed in the NPO MCHergic neurons of the hypothalamus were labeled. When MCH was microinjected into the NPO, there was a significant increase in the amount of AS (19.8 ± 1.4% versus 11.9 ± 0.2%, P < 0.05) and a significant decrease in the latency to AS (10.4 ± 4.2 versus 26.6 ± 2.3 min, P < 0.05). The preceding anatomical and functional data support our hypothesis that the MCHergic system participates in the regulation of AS by modulating neuronal activity in the NPO.