The rostromedial tegmental nucleus is essential for non-rapid eye movement sleep.

The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.

Origin of the dopaminergic innervation of adult neurogenic areas.

Adult neurogenesis, a specific form of brain plasticity in mammals occurring in the subventricular zone (SVZ) and the subgranular zone (SGZ), is subject to complex regulations. Dopamine has been identified as a regulatory factor in rodents, nonhuman primates, and humans. We therefore studied in detail the origin of the dopaminergic innervation to the SVZ and SGZ in rodents. Postmortem anterograde and retrograde tracing combined with immunofluorescence procedures indicate a topographic organization of midbrain dopaminergic projections toward the SVZ. The substantia nigra pars compacta (SNc) projects specifically into the rostral migratory stream, the anterior SVZ, and the dorsal part of the medial and posterior SVZ. In contrast, the ventral tegmental area (VTA) innervates specifically the ventral part of the medial and posterior SVZ. Both VTA and SNc dopaminergic neurons innervate homogenously the lower and upper blade of the dentate gyrus, including the SGZ. Based on these findings, we suggest that the neurogenic areas are in a position to be differentially affected by region-specific changes in dopamine signaling, the functional implication of which must be further elucidated.