Neural Control of REM Sleep and Motor Atonia: Current Perspectives

Since the formal discovery of rapid eye movement (REM) sleep in 1953, we have gained a vast amount of knowledge regarding the specific populations of neurons, their connections, and synaptic mechanisms regulating this stage of sleep and its accompanying features. This article discusses REM sleep circuits and their dysfunction, specifically emphasizing recent studies using conditional genetic tools.

Sublaterodorsal nucleus (SLD) in the dorsolateral pons, especially the glutamatergic subpopulation in this region (SLD^Glut), are shown to be indispensable for REM sleep. These neurons appear to be single REM generators in the rodent brain and may initiate and orchestrate all REM sleep events, including cortical and hippocampal activation and muscle atonia through distinct pathways. However, several cell groups in the brainstem and hypothalamus may influence SLD^Glut neuron activity, thereby modulating REM sleep timing, amounts, and architecture. Damage to SLD^Glut neurons or their projections involved in muscle atonia leads to REM behavior disorder, whereas the abnormal activation of this pathway during wakefulness may underlie cataplexy in narcolepsy. Despite some opposing views, it has become evident that SLD^Glut neurons are the sole generators of REM sleep and its associated characteristics. Further research should prioritize a deeper understanding of their cellular, synaptic, and molecular properties, as well as the mechanisms that trigger their activation during cataplexy and make them susceptible in RBD.