ArticlePloS one2014
Coupled flip-flop model for REM sleep regulation in the rat.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Sleep, Neural Circulatory Control, and Cardiovascular Disease: A Mechanistic Review.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Low-dimensional population dynamics in the brainstem gate REM sleep.Nature neuroscience · 2026Article
- Sleep Disorders in Neurodegenerative Diseases with Dementia: A Comprehensive Review.Journal of clinical medicine · 2025Review
- Article
- Selective Enhancement of REM Sleep in Male Rats through Activation of Melatonin MTThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Development of the sleep-wake switch in rats during the P2-P21 early infancy period.Frontiers in network physiology · 2023Article
- Regulation of REM sleep by inhibitory neurons in the dorsomedial medulla.Current biology : CB · 2022Article
- A probabilistic model for the ultradian timing of REM sleep in mice.PLoS computational biology · 2021Article
- Integration of sleep homeostasis and navigation in Drosophila.PLoS computational biology · 2021Article
- The Brain-Derived Neurotrophic Factor: Missing Link Between Sleep Deprivation, Insomnia, and Depression.Neurochemical research · 2020Review
- Neural and Homeostatic Regulation of REM Sleep.Frontiers in psychology · 2020Review
- Sleep Modelling across Physiological Levels.Clocks & sleep · 2019Review
- Circuit mechanisms and computational models of REM sleep.Neuroscience research · 2019Review
- A stochastic basis for neural inertia in emergence from general anaesthesia.British journal of anaesthesia · 2018Article
- Regulation of REM and Non-REM Sleep by Periaqueductal GABAergic Neurons.Nature communications · 2018Article
- Physiology of Sleep.Diabetes spectrum : a publication of the American Diabetes Association · 2016Article
- Evaluating the Evidence Surrounding Pontine Cholinergic Involvement in REM Sleep Generation.Frontiers in neurology · 2015Review
- Article
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3 authors.
Funding
Abstract
Recent experimental studies investigating the neuronal regulation of rapid eye movement (REM) sleep have identified mutually inhibitory synaptic projections among REM sleep-promoting (REM-on) and REM sleep-inhibiting (REM-off) neuronal populations that act to maintain the REM sleep state and control its onset and offset. The control mechanism of mutually inhibitory synaptic interactions mirrors the proposed flip-flop switch for sleep-wake regulation consisting of mutually inhibitory synaptic projections between wake- and sleep-promoting neuronal populations. While a number of synaptic projections have been identified between these REM-on/REM-off populations and wake/sleep-promoting populations, the specific interactions that govern behavioral state transitions have not been completely determined. Using a minimal mathematical model, we investigated behavioral state transition dynamics dictated by a system of coupled flip-flops, one to control transitions between wake and sleep states, and another to control transitions into and out of REM sleep. The model describes the neurotransmitter-mediated inhibitory interactions between a wake- and sleep-promoting population, and between a REM-on and REM-off population. We proposed interactions between the wake/sleep and REM-on/REM-off flip-flops to replicate the behavioral state statistics and probabilities of behavioral state transitions measured from experimental recordings of rat sleep under ad libitum conditions and after 24 h of REM sleep deprivation. Reliable transitions from REM sleep to wake, as dictated by the data, indicated the necessity of an excitatory projection from the REM-on population to the wake-promoting population. To replicate the increase in REM-wake-REM transitions observed after 24 h REM sleep deprivation required that this excitatory projection promote transient activation of the wake-promoting population. Obtaining the reliable wake-nonREM sleep transitions observed in the data required that activity of the wake-promoting population modulated the interaction between the REM-on and REM-off populations. This analysis suggests neuronal processes to be targeted in further experimental studies of the regulatory mechanisms of REM sleep.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.