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

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.

Yoon YS ，Lee HS 《-》

Differential distribution of melanin-concentrating hormone (MCH)- and hypocretin (Hcrt)-immunoreactive neurons projecting to the mesopontine cholinergic complex in the rat.

Hypocretin (Hcrt or orexin) and melanin-concentrating hormone (MCH) containing neurons are located in the hypothalamus and are implicated in the regulation of feeding behavior, energy homeostasis, and sleep-wake cycle. MCH and Hcrt are not co-localized within the same neuron, but these neurons project widely throughout the brain, especially to brain regions regulating arousal. Recent data indicate that HCRT and MCH neurons located medially with respect to the fornix have a differential projection pattern compared to those located lateral to the fornix. To further elucidate the projection of these neurons in the present study we use retrograde tracing methods combined with double immunofluorescence to determine the differential distribution of Hcrt- and MCH-immunoreactive neurons projecting to the pedunculopontine tegmental (PPTg) or laterodorsal tegmental (LDTg) nuclei. In rats where the retrograde tracer was confined to the PPTg/LDTg we found that there were more MCH neurons projecting to these targets compared to HCRT neurons (P<0.01). When the retrograde tracer was confined to the PPTg, there were more retrogradely labeled MCH neurons lateral to the fornix compared to MCH neurons in the medial LH subdivision (P<0.05). On the average, only about 4.5% of MCH neurons versus 6.1% of HCRT neurons project to PPTg/LDTg. Thus, very few of the MCH or HCRT neurons project to these arousal populations. Although there were significantly more MCH neurons projecting to the mesopontine cholinergic arousal zone compared to the HCRT neurons, the HCRT neurons also exert an indirect influence via the tuberomammillary nucleus. Based on the present and previous (Hong and Lee, 2011) observations, we suggest that both MCH and HCRT neurons exert a potent influence on the PPTg/LDTg, which might play an important role in arousal.

Hong EY ，Yoon YS ，Lee HS 《-》

Projection patterns of lateral hypothalamic, cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe and/or the locus coeruleus in the rat.

The present study was designed to reveal the projection patterns of lateral hypothalamic (LH), cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. After the injection of Red or Green Retrobeads into the DR or LC, LH sections were immunostained for CART and/or melanin-concentrating hormone (MCH). First, CART-immunoreactive axon terminals formed close appositions to the DR (or LC) neuronal profiles. Second, a subpopulation of CART neurons containing MCH projected to the monoaminergic nuclei; the majority of labeled neurons were observed in the dorsal hypothalamic area, the dorsal part of the posterior hypothalamic area, and the zona incerta. Cells were also observed in the perifornical part of the LH, the dorsomedial hypothalamic nucleus, the peduncular and the magnocellular parts of the LH. Of the total population of DR (or LC)-projecting cells, CART/MCH co-containing neurons were 9.5% ± 1.6% (or 10.8% ± 1.3% for LC). Finally, a subset of CART (or MCH) neurons provided divergent axon collaterals to the DR and the LC. Of the entire CART (or MCH) cell population, 3.9% ± 0.8% (or 5.6% ± 1.0% for MCH) sent axon collaterals to the DR/LC. CART/MCH co-containing neurons projecting to the DR or LC might be involved in the feeding-related regulation of arousal, stress-related responses, and emotional behaviors. Thus, CART (or MCH) cells that send divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the aminergic nuclei.

Yoon YS ，Lee HS 《-》

Opposite effects of noradrenaline and acetylcholine upon hypocretin/orexin versus melanin concentrating hormone neurons in rat hypothalamic slices.

Bayer L ，Eggermann E ，Serafin M ，Grivel J ，Machard D ，Muhlethaler M ，Jones BE ... -  《NEUROSCIENCE》

Neuropeptide Y (NPY) or cocaine- and amphetamine-regulated transcript (CART) fiber innervation on central and medial amygdaloid neurons that project to the locus coeruleus and dorsal raphe in the rat.

The amygdaloid nuclear complex has been linked to the regulation of emotional behavior and energy regulation in that emotional stress might cause either reduction or enhancement of eating. We examined hypothalamic neuronal origin of feeding/arousal-related peptidergic fibers containing cocaine- and amphetamine-regulated transcript (CART) and neuropeptide Y (NPY) located in the rat amygdala along with its efferent projections to the brainstem monoaminergic nuclei. First, central (CeA) as well as medial (MeA) amygdala, among several amygdaloid subdivisions, exhibited the most prominent NPY or CART immunostaining which consisted of a substantial number of somata as well as labeled fibers. When we examined hypothalamic neuronal origin of NPY or CART fibers projecting to the CeA and MeA, medial and lateral arcuate nuclei were neuronal origins of NPY and CART fibers, respectively. However, the majority (>70%) of amygdala-projecting CART neurons which co-contained melanin-concentrating hormone (MCH) originated from the lateral hypothalamus (LH), zona incerta (ZI), and dorsal hypothalamic area (DA). This observation implied that the CeA as well as the MeA might receive potent second-order (and downstream) feeding-related CART input from the lateral hypothalamic regions in addition to first-order CART or NPY input from the Arc. Second, a large number of CeA neurons projected to the locus coeruleus (LC), whereas only a small number of MeA cells projected to the dorsal raphe (DR); none of the CeA or MeA cells provided dual projections to the LC and DR. Finally, a portion of MCH cells in the LH, ZI, and DA sent divergent axon collaterals to the CeA and LC. Considering that the CeA sends substantial GABAergic input to the LC, the present observation might serve as an anatomical substrate to support the potent hypnogenic role of MCH neurons in the LH regions during cataplexy and REM sleep.

Hwang YG ，Lee HS 《-》