ArticlePloS one2011
Cholinergic modulation of narcoleptic attacks in double orexin receptor knockout mice.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 57 citations in OpenAlex.
- Repeated Morphine Exposure Reversibly Impairs Spike Generation and Repetitive Firing in a Functionally Distinct Subpopulation of Orexin Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice.Journal of sleep research · 2023Article
- Animal models of narcolepsy and the hypocretin/orexin system: Past, present, and future.Sleep · 2021Article
- Orexin receptor antagonists reverse aberrant dopamine neuron activity and related behaviors in a rodent model of stress-induced psychosis.Translational psychiatry · 2021Article
- Hypocretin/Orexin Receptor Pharmacology and Sleep Phases.Frontiers of neurology and neuroscience · 2021Review
- Article
- The neurobiological basis of narcolepsy.Nature reviews. Neuroscience · 2019Review
- Dual-transmitter systems regulating arousal, attention, learning and memory.Neuroscience and biobehavioral reviews · 2018Review
- The Orexin/Receptor System: Molecular Mechanism and Therapeutic Potential for Neurological Diseases.Frontiers in molecular neuroscience · 2018Review
- Rewiring brain circuits to block cataplexy in murine models of narcolepsy.Current opinion in neurobiology · 2017Review
- Challenges in the development of therapeutics for narcolepsy.Progress in neurobiology · 2017Review
- GABA Cells in the Central Nucleus of the Amygdala Promote Cataplexy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Article
- Optogenetic control of hypocretin (orexin) neurons and arousal circuits.Current topics in behavioral neurosciences · 2015Review
- Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Neurons containing orexin or melanin concentrating hormone reciprocally regulate wake and sleep.Frontiers in systems neuroscience · 2014Review
- Orexin receptor antagonists as therapeutic agents for insomnia.Frontiers in pharmacology · 2013Review
- Article
- Differential actions of orexin receptors in brainstem cholinergic and monoaminergic neurons revealed by receptor knockouts: implications for orexinergic signaling in arousal and narcolepsy.Frontiers in neuroscience · 2013Article
- Kinetic properties of "dual" orexin receptor antagonists at OX1R and OX2R orexin receptors.Frontiers in neuroscience · 2013Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
To investigate how cholinergic systems regulate aspects of the sleep disorder narcolepsy, we video-monitored mice lacking both orexin (hypocretin) receptors (double knockout; DKO mice) while pharmacologically altering cholinergic transmission. Spontaneous behavioral arrests in DKO mice were highly similar to those reported in orexin-deficient mice and were never observed in wild-type (WT) mice. A survival analysis revealed that arrest lifetimes were exponentially distributed indicating that random, Markovian processes determine arrest lifetime. Low doses (0.01, 0.03 mg/kg, i.p.), but not a high dose (0.08 mg/kg, i.p.) of the cholinesterase inhibitor physostigmine increased the number of arrests but did not alter arrest lifetimes. The muscarinic antagonist atropine (0.5 mg/kg, i.p.) decreased the number of arrests, also without altering arrest lifetimes. To determine if muscarinic transmission in pontine areas linked to REM sleep control also influences behavioral arrests, we microinjected neostigmine (50 nl, 62.5 µM) or neostigmine + atropine (62.5 µM and 111 µM respectively) into the nucleus pontis oralis and caudalis. Neostigmine increased the number of arrests in DKO mice without altering arrest lifetimes but did not provoke arrests in WT mice. Co-injection of atropine abolished this effect. Collectively, our findings establish that behavioral arrests in DKO mice are similar to those in orexin deficient mice and that arrests have exponentially distributed lifetimes. We also show, for the first time in a rodent narcolepsy model, that cholinergic systems can regulate arrest dynamics. Since perturbations of muscarinic transmission altered arrest frequency but not lifetime, our findings suggest cholinergic systems influence arrest initiation without influencing circuits that determine arrest duration.
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Registered trials
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.