Projections of the MCH System to Structures Involved in the Regulation of Sleep and Wakefulness

Abstract

Although glutamatergic sublaterodorsal tegmental nucleus (SLD) constitutes a core of rapid eye movement (REM) sleep circuits, recent reports assert that REM sleep generation is under hypothalamic control of melanin-concentrating hormone (MCH) neurons. GABAergic MCH cells control the onset and maintenance of REM sleep via direct inhibitory projection to REM-off GABAergic neurons in ventrolateral periaqueductal gray matter which exert a potent inhibitory influence on REM-on SLD cells. It is generally accepted that cholinergic neurons in the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei serve as supplementary REM-on cells, while noradrenergic locus coeruleus (LC) and serotoninergic dorsal raphe (DR) cells contribute to REM-off circuitry. MCH neurons project heavily to the PPT and LDT, where cholinergic neurons might play a role in the strengthening of non-REM (NREM) to REM transitions once initiated. They also project to the LC and DR; the microinjection of MCH into these nuclei increases REM sleep duration. Likewise, MCH neurons send efferent fibers to the tuberomammillary nucleus (TMN); the activation of these fibers prolongs REM sleep episodes. Among monoaminergic nuclei, the TMN is unique in that (1) histaminergic neurons are active in cataplexy, implying their role in the maintenance of arousal state during the period, and (2) it contains a substantial number of MCH somata within its boundary, whose physiological function remains to be established.