Ventral medullary control of rapid eye movement sleep and atonia

Abstract

Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep. Motor tone during non-REM (NREM) sleep was unaffected in these same animals. Acute chemogenetic activation of pSOM neurons in rats robustly and selectively suppressed REM sleep but not NREM sleep. Similar lesions targeting the more rostral ventromedial medulla (RVM) did not affect sleep or atonia, while chemogenetic stimulation of the RVM produced wakefulness and reduced sleep. Finally, selective activation of vesicular GABA transporter (VGAT) pSOM neurons in mice produced complete suppression of REM sleep whereas their loss increased EMG spikes during REM sleep. These results reveal a key contribution of the pSOM and specifically the VGAT+ neurons in this region in REM sleep and motor control.

Neuroscience: A Distributed Neural Network Controls REM Sleep

“…And while there is ample evidence to support this view, it is important to bear in mind that both old and recent studies have inferred the existence of at least one additional region that is important for REM sleep control. Specifically, outcomes of lesion, unit recording and chemogenetic studies have suggested an important role for the vM, including the medially located ventral gigantocellular reticular nucleus (GiV) and α-gigantocellular reticular nuclei (GiA) and laterally adjacent paragigantocellular (LPGi) cell groups, in REM sleep control and REM sleep atonia [8,107–109]. In general support of this concept, a recent optogenetic study found that activation of vM GABA neurons could potently trigger REM sleep and produce REM sleep atonia, and that this effect was likely mediated through the vlPAG-SLD circuit and direct, i.e., SLD-independent, projections to spinal motor neurons [13].…”

Targeted disruption of supraspinal motor circuitry reveals a distributed network underlying Restless Legs Syndrome (RLS)-like movements in the rat

“…Our previous work in rodents has suggested that dysfunction of pontine and medullary reticulospinal systems that support normal REM sleep atonia may underlie RLS. However, lesions of these structures that are sufficient to disturb motor activity during REM sleep do not alter motor activity during NREM sleep and sleep-wake transition periods 8 – 11 . Thus supra-pontine structures with direct projections to the spinal cord may play a more critical role in RLS, including the corticospinal tract, rubrospinal tract and hypothalamic A11 dopaminergic cell group.…”

Brainstem regulation of slow-wave-sleep

“…And similar to the identification and characterization of the SWS-promoting PZ, technical advances have enabled a more refined understanding of the cellular and synaptic basis by which a distributed network of brainstem circuits regulation REM sleep, including the recent identification of GABAergic REM-generator cells in the ventral medulla [42-45]. …”