Editing Rapid eye movement sleep (section)

=== Chemicals in the brain ===

Compared to [[slow-wave sleep]], both waking and paradoxical sleep involve higher use of the neurotransmitter [[acetylcholine]], which may cause the faster brainwaves. The  [[monoamine]] neurotransmitters [[norepinephrine]], [[serotonin]] and [[histamine]] are completely unavailable. Injections of [[acetylcholinesterase inhibitor]], which effectively increases available acetylcholine, have been found to induce paradoxical sleep in humans and other animals already in slow-wave sleep. [[Carbachol]], which mimics the effect of acetylcholine on neurons, has a similar influence. In waking humans, the same injections produce paradoxical sleep only if the monoamine neurotransmitters have already been depleted.<ref name="BrownMcCarley"/><ref name=MallickEtAl>{{cite book | vauthors = Mallick BN, Madan V, Jha S | chapter = Rapid eye movement sleep regulation by modulation of the noradrenergic system. | veditors = Monti J, Pandi-Perumal SR, Sinton CM | title = Neurochemistry of Sleep and Wakefulness. | publisher = Camibridge University Press | location = New York | date = 2008 | pages = 59–81 }}.</ref><ref name=Hobson2009>{{cite journal | vauthors = Hobson JA | title = REM sleep and dreaming: towards a theory of protoconsciousness | journal = Nature Reviews. Neuroscience | volume = 10 | issue = 11 | pages = 803–813 | date = November 2009 | pmid = 19794431 | doi = 10.1038/nrn2716 | s2cid = 205505278 }}</ref><ref name=AstonJonesEtAl>{{cite book | vauthors = Aston-Jones G, Gonzalez M, Doran S | chapter = Role of the locus coeruleus-norepinephrine system in arousal and circadian regulation of the sleep–wake cycle. | veditors =  Ordway GA, Schwartz MA, Frazer A | title = Brain norepinephrine: Neurobiology and therapeutics. | publisher = Cambridge University Press | date = February 2007 | pages = 157–195 | chapter-url = http://academicdepartments.musc.edu/neuromodulation/epapers/Aston-JonesetalLCsleepOrdway07.pdf | archive-url =  https://web.archive.org/web/20111213130015/http://academicdepartments.musc.edu/neuromodulation/epapers/Aston-JonesetalLCsleepOrdway07.pdf | archive-date=2011-12-13}}</ref><ref>{{cite book | vauthors = Siegel JM | date = 2005 | chapter = REM Sleep | title = Principles and Practice of Sleep Medicine | edition = 4th | veditors = Kryger MH, Roth T, Dement WB | publisher = Elsevier | pages = 120–135 }}</ref>

Two other [[Neurotransmitter receptor|neurotransmitters]], [[orexin]] and [[gamma-Aminobutyric acid]] (GABA), seem to promote wakefulness, diminish during deep sleep, and inhibit paradoxical sleep.<ref name=BrownMcCarley /><ref name=LuppiEtAl>{{cite book | vauthors = Luppi PH, Gervasoni D, Verret L, Goutagny R, Peyron C, Salvert D, Léger L, Fort P | date = 2008 | chapter = Gamma-aminobutyric acid and the regulation of paradoxical, or rapid eye movement, sleeps | title = Neurochemistry of Sleep and Wakefulness | veditors =  Monti J, Pandi-Perumal SR, Sinton CM | location = Cambridge | publisher = Cambridge University Press | isbn = 978-0-521-86441-1 | pages = 85–108 }}</ref>

Unlike the abrupt transitions in electrical patterns, the chemical changes in the brain show continuous periodic oscillation.<ref name=McCarley2007>{{cite journal | vauthors = McCarley RW | title = Neurobiology of REM and NREM sleep | journal = Sleep Medicine | volume = 8 | issue = 4 | pages = 302–30 | date = June 2007 | pmid = 17468046 | doi = 10.1016/j.sleep.2007.03.005 }}</ref>

==== Models of REM regulation ====

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.<ref name=BrownMcCarley /><ref name=MallickEtAl /><ref name=AstonJonesEtAl /><ref name=HobsonMcCarley1977>{{cite journal | vauthors = Hobson JA, McCarley RW | title = The brain as a dream state generator: an activation-synthesis hypothesis of the dream process | journal = The American Journal of Psychiatry | volume = 134 | issue = 12 | pages = 1335–48 | date = December 1977 | pmid = 21570 | doi = 10.1176/ajp.134.12.1335 }}</ref> They used [[Lotka–Volterra equation]]s to describe this cyclical inverse relationship.<ref name="Steriade_2013" />{{rp|§12.2 369–373}}  Kayuza Sakai and Michel Jouvet advanced a similar model in 1981.<ref name=LuppiEtAl /> Whereas acetylcholine manifests in the cortex equally during wakefulness and REM, it appears in higher concentrations in the brain stem during REM.<ref>{{cite book | vauthors = Lydic R, Baghdoyan HA | chapter = Acetylcholine modulates sleep and wakefulness: a synaptic perspective | veditors = Monti J, Pandi-Perumal SR, Sinton CM | title = Neurochemistry of Sleep and Wakefulness | date = 17 January 2008 | publisher = Cambridge University Press | isbn = 978-1-139-46789-6 }}</ref> The withdrawal of orexin and GABA  may cause the absence of the other excitatory neurotransmitters;<ref name = "Parmeggiani_2011">{{cite book | vauthors = Parmeggiani PL | date = 2011 | title = Systemic Homeostasis and Poikilostasis in Sleep: Is REM Sleep a Physiological Paradox? | location = London | publisher = Imperial College Press | isbn = 978-1-84816-572-4 }}</ref>{{rp|16}} researchers in recent years increasingly include GABA regulation in their models.<ref>{{cite book | vauthors = McKenna JT, Chen L, McCarley RW | chapter = Neuronal models of REM-sleep control: evolving concepts. | veditors = Mallick BN, Pandi-Perumal SR, McCarley RW, Morrison AR  | title = REM sleep: regulation and function | date = July 2011 | pages = 285–299 | publisher = Cambridge University Press| location = Cambridge }}</ref>