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 《-》

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 《-》

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》

Hypothalamic, feeding/arousal-related peptidergic projections to the paraventricular thalamic nucleus in the rat.

Based on the importance of paraventricular thalamic nucleus (PVT) as a relay station of energy balance, arousal, and food reward, we aimed in the present study to determine projection patterns of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH), and orexin (ORX)-ergic fibers to the PVT. First, the distribution of peptidergic axon terminals within the PVT was examined. NPY and CART terminals were confined within the boundary of the thalamic nucleus, exhibiting almost identical distribution. MCH terminals were rarely observed. In contrast, ORX terminals were as extensive as NPY/CART terminals, but spread into the peri-PVT region. Second, neuronal origin of feeding/arousal-related peptides projecting to the PVT was investigated. NPY neurons were observed in the medial subdivision of the arcuate nucleus (Arc), whereas CART cells were in the lateral Arc as well as other hypothalamic regions including the paraventricular hypothalamic nucleus, lateral hypothalamus (LH), dorsal hypothalamic area, and zona incerta. Both NPY- and CART-fiber projections to the PVT were bilateral; ipsilateral proportion was 54.0% ± 3.6% (n = 6) for NPY and 57.1% ± 2.5% (n = 6) for CART. The total number of CART neurons projecting to the PVT exceeded that of NPY cells; the ratio of labeled CART neurons to NPY cells was 2.4 ± 0.2 (n = 6). In contrast, ORX-ergic fiber projection to the PVT exhibited a slight ipsilateral dominance (62.7% ± 1.6%, n = 6), with majority of labeled cells located in the LH medial to the fornix (72.2% ± 2.3%, n = 6). Third, based on heavy projection from the PVT to the nucleus accumbens shell (NAcSh), the convergence of NPY and CART terminals on a single PVT neuron was identified; the proportion of labeled PVT neurons that received converging NPY/CART terminals compared with the total PVT neurons projecting to the NAcSh was 2.7% ± 0.6% (n = 3). Finally, PVT cells receiving NPY, CART, or ORX terminals provided divergent axon collaterals to NAcSh and medial prefrontal cortex. The present observations provided the anatomical evidence that the PVT might play an essential role in the integration of antagonistically-acting, feeding/arousal-related peptidergic inputs on their way to the cortical reward circuit.

Lee JS ，Lee EY ，Lee HS 《-》

Retrograde study of projections from the tuberomammillary nucleus to the mesopontine cholinergic complex in the rat.

The mesopontine cholinergic complex comprising the pedunculopontine (PPTg) and laterodorsal (LDTg) tegmental nuclei is a key component of ascending reticular activating system. The brainstem cholinergic nuclei are yet under the control of descending projections from hypothalamic arousal centers such as the hypocretinergic, lateral hypothalamus (LH), and the histaminergic, tuberomammillary nucleus (TMN). The present study was designed to determine the differential projection pattern as well as the laterality of descending TMN projections to the PPTg and LDTg. Our results showed that each TMN subdivision provided differential projections to the mesopontine complex. The majority of PPTg-projecting neurons were located in ventrolateral TMN mainly at its subpial border, whereas LDTg-projecting cells were in dorsomedial TMN with a few in the medial border of the ventrolateral subdivision. For both PPTg and LDTg cases, retrogradely labeled neurons were more pronounced in each TMN subdivision ipsilateral to the injection site. The light microscopic observation also indicated that hypocretinergic, terminal-like boutons formed close appositions to somata as well as proximal dendrites of PPTg- or LDTg-projecting TMN neurons. Taken together, the present observations suggested that each TMN subdivision provide differential projections to the mesopontine cholinergic complex and that the LH, via the TMN, provides indirect, descending projections to the complex as well.

Hong EY ，Lee HS 《-》