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 《-》

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 《-》

Retrograde study of projections from the tuberomammillary nucleus to the dorsal raphe and the locus coeruleus in the rat.

Lee HS ，Lee BY ，Waterhouse BD 《BRAIN RESEARCH》

Organization of histamine-immunoreactive, tuberomammillary neurons projecting to the dorsal tier of the substantia nigra compacta in the rat.

Lee SB ，Chang BJ ，Lee HS 《BRAIN RESEARCH》

Collateral projection from the forebrain and mesopontine cholinergic neurons to whisker-related, sensory and motor regions of the rat.

The primary goal of this anatomical study was to examine in the rat whether cholinergic neurons provide axon collaterals to whisker-related, sensorimotor regions at cortical, thalamic, and brainstem levels, using a combined method of retrograde tracing and choline acetyltransferase (ChAT) immunostaining. First, when injections were made at primary sensory (S1) barrel field/primary whisker motor (M1) cortices, cholinergic neurons with dual projections were observed in the basal nucleus of Meynert (BM), mainly at middle level; the projection was almost exclusively ipsilateral (99%+/-0.7%, n=6). Second, following unilateral injections of tracers into ventroposteromedial (VPM) barreloids/ventrolateral (VL) thalamic nucleus, dual-projecting cells were observed in the mesopontine tegmental complex including the pedunculopontine tegmental (PTg) and laterodorsal tegmental (LDTg) nuclei, mainly at rostral to middle levels; the projection exhibited ipsilateral dominance, i.e., 67%+/-1.3% (n=6) for the PTg and 64%+/-1.2% (n=6) for the LDTg. Finally, when injections were made at whisker-related, principal sensory trigeminal (Pr5)/facial motor (Mo7) nuclei, a relatively small number of labeled neurons were observed in the PTg and the LDTg at middle to caudal levels; within LDTg, labeled cells occupied the ventral portion of the dorsal LDTg as well as the ventral LDTg (LDTgV). This projection exhibited contralateral preponderance, i.e., 67%+/-2.0% (n=6) for the PTg and 69%+/-3.2% (n=6) for the LDTg. Taken together, the present observations demonstrated that each division of the BM, PTg, and LDTg possessed a differential functional organization with respect to its collateral projection to whisker-related sensorimotor targets, suggesting that the cholinergic projection might play a modulatory role in vibrissal sensorimotor integration, which allows the guidance of behavioral action essential for the survival of the animal.

Beak SK ，Hong EY ，Lee HS 《-》