The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell groups in regulating cortical activity and behavioral state remain unknown. Using a chemogenetic approach in three Cre-driver mouse lines, we found that selective activation of glutamatergic PPT neurons induced prolonged cortical activation and behavioral wakefulness, whereas inhibition reduced wakefulness and increased non-REM (NREM) sleep. Activation of cholinergic PPT neurons suppressed lower-frequency electroencephalogram rhythms during NREM sleep. Last, activation of GABAergic PPT neurons slightly reduced REM sleep. These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially influence cortical activity and sleep/wake states.SIGNIFICANCE STATEMENTMore than 40 million Americans suffer from chronic sleep disruption, and the development of effective treatments requires a more detailed understanding of the neuronal mechanisms controlling sleep and arousal. The pedunculopontine tegmental (PPT) nucleus has long been considered a key site for regulating wakefulness and REM sleep. This is mainly because of the cholinergic neurons contained in the PPT nucleus. However, the PPT nucleus also contains glutamatergic and GABAergic neurons that likely contribute to the regulation of cortical activity and sleep–wake states. The chemogenetic experiments in the present study reveal that cholinergic, glutamatergic, and GABAergic PPT neurons each have distinct effects on sleep/wake behavior, improving our understanding of how the PPT nucleus regulates cortical activity and behavioral states.

Adequate sleep quantity and quality is required to maintain vigilance, cognitive and learning processes. A decrease of sleep quantity preflight and on the International Space Station (ISS) has been reported. Recent counter-measures have been implemented to better regulate sleep opportunities on ISS. In our study, astronauts were allocated enough time for sleep the night before the recordings. However, for proper sleep recovery, the quality of sleep is also critical. Unfortunately, data on sleep quality have yet to be acquired from the ISS. Here, we investigate sleep pressure markers during wakefulness in five astronauts throughout their 6-month space mission by the mean of electroencephalographic recordings. We show a global increase of theta oscillations (5–7 Hz) on the ISS compared to on Earth before the mission. We also show that local sleep-like events, another marker of sleep pressure, are more global in space (p < 0.001). By analysing the performances of the astronauts during a docking simulation, we found that local sleep-like events are more global when reaction times are slower (R² = 0.03, p = 0.006) and there is an increase of reaction times above 244 ms after 2 months in space (p = 0.012). Our analyses provide first evidence for increased sleep pressure in space and raise awareness on possible impacts on visuomotor performances in space.