A Mathematical Model towards Understanding the Mechanism of Neuronal Regulation of Wake-NREMS-REMS States
Open Access
- 8 August 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (8), e42059
- https://doi.org/10.1371/journal.pone.0042059
Abstract
In this study we have constructed a mathematical model of a recently proposed functional model known to be responsible for inducing waking, NREMS and REMS. Simulation studies using this model reproduced sleep-wake patterns as reported in normal animals. The model helps to explain neural mechanism(s) that underlie the transitions between wake, NREMS and REMS as well as how both the homeostatic sleep-drive and the circadian rhythm shape the duration of each of these episodes. In particular, this mathematical model demonstrates and confirms that an underlying mechanism for REMS generation is pre-synaptic inhibition from substantia nigra onto the REM-off terminals that project on REM-on neurons, as has been recently proposed. The importance of orexinergic neurons in stabilizing the wake-sleep cycle is demonstrated by showing how even small changes in inputs to or from those neurons can have a large impact on the ensuing dynamics. The results from this model allow us to make predictions of the neural mechanisms of regulation and patho-physiology of REMS.This publication has 88 references indexed in Scilit:
- REM sleep loss increases brain excitability: Role of noradrenalin and its mechanism of actionSleep Medicine Reviews, 2011
- Orexin/Hypocretin and Histamine: Distinct Roles in the Control of Wakefulness Demonstrated Using Knock-Out Mouse ModelsJournal of Neuroscience, 2009
- Sleep deprivation in a quantitative physiologically based model of the ascending arousal systemJournal of Theoretical Biology, 2008
- Delayed Orexin Signaling Consolidates Wakefulness and Sleep: Physiology and ModelingJournal of Neurophysiology, 2008
- Clinical and neurobiological aspects of narcolepsySleep Medicine, 2007
- Mathematical Model of Network Dynamics Governing Mouse Sleep–Wake BehaviorJournal of Neurophysiology, 2007
- Role of noradrenergic and GABA-ergic inputs in pedunculopontine tegmentum for regulation of rapid eye movement sleep in ratsNeuropharmacology, 2006
- Role of alpha and beta adrenoceptors in locus coeruleus stimulation-induced reduction in rapid eye movement sleep in freely moving ratsBehavioural Brain Research, 2005
- Long term blocking of GABA-A receptor in locus coeruleus by bilateral microinfusion of picrotoxin reduced rapid eye movement sleep and increased brain Na–K ATPase activity in freely moving normally behaving ratsBehavioural Brain Research, 2004
- Influence of hypnogenic brain areas on wakefulness- and rapid-eye-movement sleep-related neurons in the brainstem of freely moving catsJournal of Neuroscience Research, 2003