Crossing the Line: Factors Associated With Escalating Pornography Use.

REMs is an “active” phase of sleep, hallmarked by prominent EMs. During REMs, postural motor neurons are inhibited, and muscles are relaxed, with the exception of EOMs. As a prominent pool of cholinergic neurons within the midbrain, the oculomotor nucleus (nIII) has been suggested to modulate oculomotility, not only during wakefulness but also during REMs, although there are some discrepancies. In alert animals, spontaneous EMs consist of voluntary and involuntary saccades that move and keep the eyes to a visual target, enabling visual acquisition. These modalities of EMs are coordinated by nIII and other nuclei, the trochlear nucleus, and the abducent nucleus. Specifically, abducting and adducting EMs are mediated by motoneurons in the abducens nucleus and nIII, respectively, whereas the torsional rotation of the eyeball is controlled by the trochlear nucleus via its innervation of the superior oblique muscle. With regard to EMs in sleep, Herrera et al. provided evidence that the activation of the nIII is responsible for the occurrence of EMs during REMs, spawning new data on the behavior of this visuomotor system during sleep. Ludwig Mauthner postulated the existence of a putative “sleep center” situated near the nIII within the midbrain. Since then, multiple nuclei in close proximity to the nIII have been identified as potential regulators of sleep, such as GABAergic neurons in the dorsal norepinephrine bundle, cholinergic neurons in the laterodorsal tegmentum (LDT) in the genesis of REMs, as well as the glutamatergic neurons in the dorsal deep mesencephalic nucleus (dDpMe) in the promotion of NREM sleep (NREMs). A recent study identified sleep-active neurons within the perioculomotor (pIII) region and Edinger-Westphal nucleus (EWcp), both of which were adjacent to the nIII. It was found that activating Calca neurons in the pIII region or activating GHSR signaling in EWcp facilitates NREMs. Meanwhile, the nIII has abundant afferent connections with the midbrain reticular formation, a key regulator of REMs. Cholinergic neurons within the nIII displayed progressively augmented activity with increasing REM sleep deprivation duration, as evidenced by a marked increase in c-Fos expression in nIII neurons. These findings suggest that nIII neurons might play an important role in regulating both vigilance states and EMs. However, the definite functional role of nIII neurons in sleep regulation is yet to be studied. Here, we first observed the elevated c-Fos expression of nIII neurons during recovery sleep after deprivation in mice. Using fiber photometry and an electrophysiological approach, we identified a population of cholinergic neurons in the nIII that are active in response to repeated REM-to-wake (R-W) transitions. Calcium imaging revealed that those neurons were functionally distinct from the oculomotoneurons and formed a densely interconnected network. Viral tracing experiments revealed that, distinct from extraocular muscles (EOMs)-projecting nIII neurons, this newly identified nIII projects to the ventrolateral periaqueductal gray (vlPAG). We then selectively inhibited and activated these nIII neurons to investigate their involvement in sleep regulation. Finally, using optogenetics-assisted electrophysiological recording combined with a retrograde labeling approach, we unveiled that the upstream nucleus papilio (NP) functions as an initiator. The NP-nIII-EOMs pathway is responsible for oculomotility in REMs, whereas the NP-nIII-vlPAG circuit gates the switch of REMs. Taken together, our results implicate the functional diversity of nIII neurons and underscore the dual role of the nIII in motor function and REMs regulation mediated by distinct subsets of cholinergic neurons.