According to the activation-synthesis hypothesis proposed by Robert McCarley and Allan Hobson in 1975–1977, control over REM sleep involves pathways of "REM-on" and "REM-off" neurons in the brain stem. REM-on neurons are primarily cholinergic (i.e., involve acetylcholine); REM-off neurons activate serotonin and noradrenaline, which among other functions suppress the REM-on neurons. McCarley and Hobson suggested that the REM-on neurons actually stimulate REM-off neurons, thereby serving as the mechanism for the cycling between REM and non-REM sleep. They used Lotka–Volterra equations to describe this cyclical inverse relationship. Kayuza Sakai and Michel Jouvet advanced a similar model in 1981. Whereas acetylcholine manifests in the cortex equally during wakefulness and REM, it appears in higher concentrations in the brain stem during REM. The withdrawal of orexin and GABA may cause the absence of the other excitatory neurotransmitters; researchers in recent years increasingly include GABA regulation in their models.
According to the activation-synthesis hypothesis proposed by Robert McCarley and Allan Hobson in 1975–1977, control over REM sleep involves pathways of "REM-on" and "REM-off" neurons in the brain stem. REM-on neurons are primarily cholinergic (ie., involve acetylcholine); REM-off neurons activate serotonin and noradrenaline, which among other functions suppress the REM-on neurons. McCarley and Hobson suggested that the REM-on neurons actually stimulate REM-.off neurons, thereby serving as the mechanism for the cycling between REM and non-REM sleep. They used Lotka–Volterra equations to describe this cyclical inverse relationship. Kayuza Sakai and Michel Jouvet advanced a similar model in 1981. Whereas acetylcholine manifests in the cortex equally during wakefulness and REM, it appears in higher concentrations in the brain stem during REM. The withdrawal of orexin and GABA may cause the absence of the other excitatory neurotransmitters; researchers in recent years increasingly include GABA regulation in their models.