GABAergic neurons in the rostromedial tegmental nucleus are essential for rapid eye movement sleep suppression.

Rapid eye movement (REM) sleep disturbances are prevalent in various psychiatric disorders. However, the neural circuits that regulate REM sleep remain poorly understood. Here, we found that in male mice, optogenetic activation of rostromedial tegmental nucleus (RMTg) GABAergic neurons immediately converted REM sleep to arousal and then initiated non-REM (NREM) sleep. Conversely, laser-mediated inactivation completely converted NREM to REM sleep and prolonged REM sleep duration. The activity of RMTg GABAergic neurons increased to a high discharge level at the termination of REM sleep. RMTg GABAergic neurons directly converted REM sleep to wakefulness and NREM sleep via inhibitory projections to the laterodorsal tegmentum (LDT) and lateral hypothalamus (LH), respectively. Furthermore, LDT glutamatergic neurons were responsible for the REM sleep-wake transitions following photostimulation of the RMTgGABA-LDT circuit. Thus, RMTg GABAergic neurons are essential for suppressing the induction and maintenance of REM sleep.

Whole-Brain Monosynaptic Afferents to Rostromedial Tegmental Nucleus Gamma-Aminobutyric Acid-Releasing Neurons in Mice.

Increasing evidence has revealed that the rostromedial tegmental area (RMTg) mediates many behaviors, including sleep and addiction. However, presynaptic patterns governing the activity of γ-aminobutyric acid-releasing (GABAergic) neurons, the main neuronal type in the RMTg, have not been defined. Here, we used cell-type-specific retrograde trans-synaptic rabies viruses to map and quantify the monosynaptic afferents to RMTg GABAergic neurons in mouse whole brains. We identified 71 ascending projection brain regions. Sixty-eight percent of the input neurons arise from the ipsilateral and 32% from the contralateral areas of the brain. The first three strongest projection regions were the ipsilateral lateral hypothalamus, zone incerta, and contralateral pontine reticular nucleus. Immunohistochemistry imaging showed that the input neurons in the dorsal raphe, laterodorsal tegmentum, and dorsal part of zone incerta were colocalized with serotoninergic, cholinergic, and neuronal nitric oxide synthetase-expressing neurons, respectively. However, in the lateral hypothalamus, a few input neurons innervating RMTg GABAergic neurons colocalized orexinergic neurons but lacked colocalization of melanin-concentrating hormone neurons. Our findings provide anatomical evidence to understand how RMTg GABAergic neurons integrate diverse information to exert varied functions.