Journal Article

Brainstem and Spinal Cord Circuitry Regulating REM Sleep and Muscle Atonia

Vetrivelan, Ramalingam, Lowell, Bradford B., Fuller, Patrick M., Krenzer, Martina, Wang, Nishang, Vong, Linh, Lu, Jun, Anaclet, Christelle

2011

Overview

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).

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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