Cholinergic involvement in control of REM sleep paralysis

Abstract

REM sleep, also known as dreaming sleep, is marked by intense cortical activation and absence of skeletal muscle tone, so-called REM sleep paralysis (atonia). It is commonly believed that REM sleep paralysis functions to prevent movement during vivid dreams. Indeed, REM sleep behaviour disorder -a neurological condition marked by violent dream enactment -results from loss of REM sleep paralysis. For the last 50 years, biologists have focused on the identification of brain mechanisms responsible for REM sleep. A majority of evidence suggests that a brainstem region known as the sublaterodorsal nucleus (SLD), also called the subcoeruleus, is important for REM sleep generation (Jouvet 1962). However, there is uncertainty concerning the chemical mechanisms by which the SLD triggers REM sleep phenomena. For example, some data suggest that cholinergic modulation of SLD cells underlies REM sleep generation, whereas, other data suggest that GABAergic disinhibition and glutamatergic excitation of SLD cells are critical for REM sleep control (Boissard et al. 2002;Lu et al. 2006). The recent study by Weng et al. (2014) provides a potentially new framework for understanding REM sleep control by showing that both cholinergic and glutamatergic processes operating within the SLD could be important for triggering REM sleep paralysis. The SLD contains cells that are crucial for generating REM sleep paralysis. Pharmacological and electrical activation of SLD neurons produces a REM-like Z.A. Torontali and K.P. Grace contributed equally to this manuscript sleep state that is characterized by muscle paralysis and cortical activation. In contrast, SLD lesions produce REM sleep without atonia in animals, and neurodegeneration of the SLD region is associated with REM sleep behaviour disorder in humans. REM sleep-active SLD neurons are glutamatergic and are thought to induce REM paralysis by activating GABA and glycine-containing neurons in the ventromedial medulla and spinal cord, which in turn trigger motor atonia by inhibiting skeletal motoneurons (Boissard et al. 2002). During REM sleep, acetylcholine is thought to participate in the activation of these descending atonia pathways. For example, application of cholinergic agonists into the SLD can induce long-lasting periods of cortical activation and muscle paralysis (Steriade & McCarley, 2005). Nevertheless, not all experimental interventions produce this same effect. In fact, cholinergic stimulation of the SLD can also induce prolonged bouts of wakefulness (George et al. 1964). Taking these contradictions to heart, Weng and co-workers set out to understand better how cholinergic mechanisms regulate REM sleep paralysis at the level of the SLD.Because the SLD contains a heterogeneous pool of neurons that mediate a range of behaviours, Weng and co-workers developed a new approach for studying how cholinergic mechanisms affect the function of spinally projecting SLD neurons specifically. They did this by retrogradely labelling SLD neurons from the spinal cord and then used in vitro ele...

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