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"A putative flip–flop switch for control of REM sleep", Nature

June 1, 2006

Authors Jun Lu, David Sherman, Marshall Devor and Clifford B Saper published a lead Article, "A putative flip-flop switch for control of REM sleep", in the journal Nature in June 2006, describing for the first time a model for how the brain controls REM sleep.  This model involves a flip-flop switch that controls transitions into and out of REM sleep, and describes two new pathways, one from the REM-on area to the spinal cord, which the authors believe controls REM sleep loss of muscle tone, and the other from the REM-on area to the basal forebrain, which the authors believe controls the EEG and dream state.

Lu J, Sherman D, Devor M, Saper CB. A putative flip-flop switch for control of REM sleep. Nature. 2006 Jun 1;441(7093):589-94. PMID: 16688184


Rapid eye movement (REM) sleep consists of a dreaming state in which there is activation of the cortical and hippocampal electroencephalogram (EEG), rapid eye movements, and loss of muscle tone. Although REM sleep was discovered more than 50 years ago, the neuronal circuits responsible for switching between REM and non-REM (NREM) sleep remain poorly understood. Here we propose a brainstem flip–flop switch, consisting of mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum. Each side contains GABA (gamma-aminobutyric acid)-ergic neurons that heavily innervate the other. The REM-on area also contains two populations of glutamatergic neurons. One set projects to the basal forebrain and regulates EEG components of REM sleep, whereas the other projects to the medulla and spinal cord and regulates atonia during REM sleep. The mutually inhibitory interactions of the REM-on and REM-off areas may form a flip–flop switch that sharpens state transitions and makes them vulnerable to sudden, unwanted transitions—for example, in narcolepsy.

Related Links:
Link to publication on Nature website
Important new discoveries in neurobiology of sleep

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