Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia

Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM) sleep. To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuit...

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Bibliographic Details
Published in:PloS one 2011-10, Vol.6 (10), p.e24998-e24998
Main Authors: Krenzer, Martina, Anaclet, Christelle, Vetrivelan, Ramalingam, Wang, Nishang, Vong, Linh, Lowell, Bradford B, Fuller, Patrick M, Lu, Jun
Format: Article
Language:English
Subjects:
Animals
Behavior disorders
Biology
Brain stem
Brain Stem - physiology
Cats
Circuits
Cre recombinase
Etiology
Eye
Eye movements
GABA
GABAergic Neurons
Glutamate
Glutamatergic transmission
Glutamic Acid
Glutamic acid transporter
Glycine
Glycine transporter
In vivo methods and tests
Interneurons
Laterodorsal tegmental nucleus
Liquid oxygen
Medical research
Medicine
Mice
Muscle Hypotonia - physiopathology
Neurology
Neurons
Neurotransmitters
Nuclei
Parkinson's disease
Periaqueductal gray area
Population
Recombinase
REM sleep
Rodents
Sleep
Sleep (REM)
Sleep - physiology
Sleep disorders
Sleep, REM - physiology
Spinal cord
Spinal Cord - physiology
Substantia grisea
Tegmental nucleus
Tegmentum
Ventral horn
Vesicular Glutamate Transport Protein 2
Vesicular Inhibitory Amino Acid Transport Proteins
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Summary:Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM) sleep. To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre) into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2) or vesicular GABA-glycine transporter (VGAT) genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD) and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT) and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG) and lateral pontine tegmentum (LPT) are not critically involved in REM sleep control. These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD).
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0024998