Projections from melanin-concentrating hormone (MCH) neurons to the dorsal raphe or the nuclear core of the locus coeruleus in the rat

Abstract

Brainstem aminergic and cholinergic nuclei are essential components of reticular activating system which are under the control of hypothalamic sleep/arousal centers. In contrast to well-known role of hypocretin (Hcrt) as a potent wake-promoting substance, only recent reports stated that melanin-concentrating hormone (MCH) plays a role in the maintenance of rapid eye movement (REM) sleep. As the sequel to our report concerning the MCH/Hcrt projection to the brainstem cholinergic nuclei (Hong et al., 2011), in the present study we examined the differential projection from MCH/Hcrt neurons in medial and lateral subdivisions of the lateral hypothalamus (LH) to the dorsal raphe (DR) or the nuclear core of the locus coeruleus (LC) of the rat. Following the injection of Red Retrobeads into the LC core (n=6), the proportions of retrogradely labeled (retro-) MCH neurons over the total retro-cells were 4.4%±0.5% (medial subdivision) and 7.4%±0.6% (lateral one), whereas those of retro-Hcrt cells over the total retro-cells were 69.4%±3.6% (medial) and 64.4%±5.2% (lateral). Following midline-DR injections (n=6), the proportions of retro-MCH neurons over the total retro-cells were 14.3%±2.9% (medial) and 12.3%±1.6% (lateral), while those of retro-Hcrt cells over the total retro-cells were 46.5%±6.2% (medial) and 51.3%±9.5% (lateral). Following lateral wing-DR injections (n=3), the proportions of retro-MCH neurons over the total retro-cells were 15.5%±1.2% (medial) and 11.9%±3.1% (lateral), while those of retro-Hcrt cells over the total retro-cells were 48.5%±2.7% (medial) and 52.8%±2.3% (lateral). The statistical analysis showed that MCH neurons projecting to the LC core or DR were outnumbered by Hcrt cells (P<0.01) and that retro-MCH cells exhibited lateral predominance in LC injection cases (P<0.05). Based on our present as well as previous (Hong et al., 2011) observations, we suggested that MCH and Hcrt neurons in the LH provide preferential projections to the brainstem cholinergic and aminergic nuclei, respectively and that MCH projections to the nuclear core of the LC exhibit differential distribution within LH subdivisions.