Selective inhibition of rem sleep-active pedunculopontine tegmental neurons suppresses respiratory network activity and REM sleep expression

Abstract

Event Abstract Back to Event Selective inhibition of rem sleep-active pedunculopontine tegmental neurons suppresses respiratory network activity and REM sleep expression Kevin P. Grace1*, H. Liu1, 2 and Richard L. Horner1, 2 1 University of Toronto, Department of Physiology, Canada 2 University of Toronto, Department of Medicine, Canada Introduction: Rapid eye movement (REM) sleep is one of the three phenomenologically distinct and naturally occurring states of the mammalian central nervous system; associated with heightened neural activity and the inhibition of motor output pathways. During REM sleep, respiratory rate and variability are increased and the activity of certain respiratory muscles (e.g., genioglossus muscle of the tongue) is suppressed, with these changes defining the respiratory phenotype of REM sleep. Hypothesis: Based on several lines of new evidence which challenge the prevailing notion that pedunculopontine tegmental (PPT) neurons generate REM sleep, we hypothesize that selective inhibition of PPT REM sleep-active neurons will indicate that this cell group functions to suppresses REM sleep as well as shape its respiratory phenotype. Methods: This study used a combination of reverse microdialysis, electrophysiology, NADPH-diaphorase histochemistry and pharmacological methods in freely behaving rats (n=30) chronically instrumented for recording of sleep-wake states and respiratory muscle activities. Results: Bilateral perfusion of 8-OH-DPAT (10µM) into the PPT nuclei in order to selectively inhibit REM sleep-active neurons resulted in increased transitioning between sleep-wake states (P<0.001; normalized increase in transitions/hr = 76%) and a 15% reduction (P<0.001) of time spent in wakefulness predominantly accounted for by an increase in REM sleep. This increase in REM sleep propensity is reflected in the finding that the proportion of total sleep time occupied by REM sleep increased by 7.3% (P=0.017) during 8-OH-DPAT perfusion. Across all sleep-wake states, 8-OH-DPAT produced a significant increase in respiratory rate (P=0.003; mean increase = 7.3 breaths/min) and respiratory-related genioglossus activity (P=0.027; mean normalized increase = 69%). Given that a subset of PPT neurons are cholinergic, the latter effect may be due to withdrawal of direct cholinergic inhibition of the hypoglossal motor nucleus (HMN), which innervates the genioglossus muscle, since increasing endogenous acetylcholine at the HMN via microdialysis perfusion of an acetylcholinesterase inhibitor (100µM - eserine) resulted in significant suppression of respiratory-related genioglossus activity across sleep-wake states (P=0.008; mean normalized decrease = 56%). Conclusions: The PPT REM sleep-active cell population has a necessary role in shaping the phenotype of breathing via tonic suppression of respiratory rate and genioglossus muscle activity. Additionally, these neurons are critically involved in shaping sleep-wake state architecture; acting to suppress REM sleep, maintain wakefulness, and limit sleep-wake state transitioning. Current models regard the PPT nucleus as a generator of REM sleep on the basis of circumstantial evidence and therefore current models ought to be amended to reflect these direct findings. Acknowledgements: This research was supported by the CIHR K.G. is supported by a Graduate Studentship from the Ontario Thoracic Society Conference: B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Grace KP, Liu H and Horner RL (2009). Selective inhibition of rem sleep-active pedunculopontine tegmental neurons suppresses respiratory network activity and REM sleep expression. Front. Neurosci. Conference Abstract: B.R.A.I.N. platform in Physiology poster day 2009. doi: 10.3389/conf.neuro.03.2009.17.033 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Dec 2009; Published Online: 17 Dec 2009. * Correspondence: Kevin P Grace, University of Toronto, Department of Physiology, Toronto, Canada, kevin.grace@utoronto.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kevin P Grace H. Liu Richard L Horner Google Kevin P Grace H. Liu Richard L Horner Google Scholar Kevin P Grace H. Liu Richard L Horner PubMed Kevin P Grace H. Liu Richard L Horner Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.