Glutamatergic regulation of REM sleep

Since the discovery of rapid eye movement (REM) sleep (also known as paradoxical sleep, PS), it has been accepted that sleep is an active process. Paradoxical sleep is characterized by electroencephalogram (EEG) rhythmic activity resembling that of waking with a disappearance of muscle tone and the occurrence of REMs in contrast to slow-wave sleep (SWS, also known as non-REM sleep) identified by the presence of delta waves. Here, we review the most recent data indicating that glutamatergic neurons play a key role in the genesis of PS. We propose an updated integrated model of the mechanisms responsible for PS integrating these neurons. We hypothesize that the entrance from SWS to PS is due to the activation of PS-active glutamatergic neurons localized in the pontine sublaterodorsal tegmental nucleus (SLD). We further propose that these neurons are tonically excited across all the sleep–waking cycle by glutamatergic neurons localized in the lateral periaqueductal gray. We finally hypothesize that the onset of activity of the SLD glutamatergic neurons is due to the removal of a GABAergic input from neurons localized in the ventrolateral periaqueductal gray and the adjacent deep mesencephalic reticular nucleus.