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This Article Full Text Full Text (PDF) All Versions of this Article: 584/3/735    most recent jphysiol.2007.140160v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fuller, P. M. Articles by Lu, J. Search for Related Content PubMed PubMed Citation Articles by Fuller, P. M. Articles by Lu, J. Related Collections Review articles

¹ Department of Neurology, Division of Sleep Medicine, and Program in Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

Rapid eye movement (REM) sleep is a behavioural state characterized by activation of the cortical and hippocampal EEG, rapid eye movements and muscle atonia. For the past 30 years, the most widely accepted neural circuitry model for the regulation of REM sleep has emphasized reciprocal inhibitory interactions between pontine brainstem monoaminergic and cholinergic neurons. In general support of the reciprocal interaction model, neuropharmacological studies have shown that cholinergic agonists promote REM sleep and muscarinic antagonists and monoamines inhibit REM sleep. It has nevertheless proven difficult to reconcile both the theoretical framework of this model and the pharmacological data with the fact that selective lesions of either cholinergic or monoaminergic (noradrenergic, serotoninergic or dopaminergic) nuclei in the brainstem have relatively limited effects on REM sleep. Recent work by our laboratory has revealed the presence of non-cholinergic and non-monoaminergic mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum that may form the neuroanatomical basis of the switching circuitry for REM sleep. These findings posit a REM switching circuitry model that is analogous to an electronic ‘flip-flop’ switch. In this flip-flop switch arrangement, GABAergic REM-on neurons (located in the sublaterodorsal tegmental nucleus (SLD)) inhibit GABAergic REM-off neurons (located in the ventrolateral periaqueductal grey matter (vlPAG) and lateral pontine tegmentum (LPT)) and vice versa. In the REM-on area are two populations of glutamatergic neurons, the first of which projects to the basal forebrain and regulates EEG components of REM sleep and the second of which projects to the ventromedial medulla and spinal cord and regulates atonia during REM sleep. Our findings demonstrating independent pathways mediating atonia and the EEG components of REM provide a basis for their occasional dissociation in pathological states, e.g. REM sleep behaviour disorder.

(Received 4 July 2007; accepted after revision 17 September 2007; first published online 20 September 2007)
Corresponding author J. Lu: Department of Neurology, Division of Sleep Medicine, and Program in Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Email: jlu{at}bidmc.harvard.edu