Medullary circuitry regulating rapid eye movement sleep and motor atonia.
Considerable data support a role for glycinergic ventromedial medulla neurons in the mediation of the postsynaptic inhibition of spinal motoneurons necessary for the motor atonia of rapid-eye movement (REM) sleep in cats. These data are, however, difficult to reconcile with the fact that large lesions of the rostral ventral medulla do not result in loss of REM atonia in rats. In the present study, we sought to clarify which medullary networks in rodents are responsible for REM motor atonia by retrogradely tracing inputs to the spinal ventral horn from the medulla, ablating these medullary sources to determine their effects on REM atonia and using transgenic mice to identify the neurotransmitter(s) involved. Our results reveal a restricted region within the ventromedial medulla, termed here the "supraolivary medulla" (SOM), which contains glutamatergic neurons that project to the spinal ventral horn. Cell-body specific lesions of the SOM resulted in an intermittent loss of muscle atonia, taking the form of exaggerated phasic muscle twitches, during REM sleep. A concomitant reduction in REM sleep time was observed in the SOM-lesioned animals. We next used mice with lox-P modified alleles of either the glutamate or GABA/glycine vesicular transporters to selectively eliminate glutamate or GABA/glycine neurotransmission from SOM neurons. Loss of SOM glutamate release, but not SOM GABA/glycine release, resulted in exaggerated muscle twitches during REM sleep that were similar to those observed after SOM lesions in rats. These findings, together, demonstrate that SOM glutamatergic neurons comprise key elements of the medullary circuitry mediating REM atonia.
Vetrivelan
Ramalingam
R
Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Fuller
Patrick M
PM
Tong
Qingchun
Q
Lu
Jun
J
D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009068:Movement / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D013997:Time Factors; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine