Waoefulness NLS-4 nor modafinil induced promotihg Antioxidant fruits for digestive health, stereotypic Athletic performance optimization, or abnormal behavior by direct observation, wakefuoness promoting wakefulness video Antioxidant fruits for digestive health. Optogenetic disruption of sleep continuity impairs memory consolidation. The Faculty of Life Sciences and the Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel. NREM sleep can be further subdivided into three stages. Together, these data show that the OX2R in the VLPO partially mediates the effects of orexin-A on SPA. Natural neural projection dynamics underlying social behavior. ISBN

Promoting wakefulness -

PMID S2CID The Primary Care Companion to the Journal of Clinical Psychiatry. PMC Stahl's Illustrated Antidepressants. Cambridge University Press. ISBN British Journal of Pharmacology. Sleep Medicine. Clinical Neuropharmacology. SUNOSI® for Patients".

Retrieved Environmental Health and Toxicology. Adapromine Amantadine Bromantane Memantine Rimantadine. Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Levopropylhexedrine Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane.

CX CX CX CX CX IDRA LY, LY, Nooglutyl Org PEPA S Sunifiram Unifiram. Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine. A, A, ABT ABT AR-R Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS Ispronicline Nicotine PHA, PNU, PNU, Pozanicline Rivanicline Sazetidine A SIBA SSR, TC TC TC Tebanicline UB Varenicline WAY, Anatoxin-a Bicuculline DMCM Flurothyl Gabazine Pentetrazol Picrotoxin Strychnine Thujone.

Adrafinil Armodafinil CRL, CRL, Fluorenol Modafinil. Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide. ATC code : N06B. Categories : Drug classes defined by psychological effects Nootropics. Hidden categories: Articles with short description Short description is different from Wikidata.

Toggle limited content width. Drug class. In Wikidata. The CME Institute of Physicians Postgraduate Press, Inc. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physician assistants may receive a maximum of 0. To obtain credit for this activity, study the material and complete the CME Posttest and Evaluation. The latest review of this material was January In spite of the high prevalence of insomnia and other sleep disorders, especially chronic sleep disorders, current treatments are imperfect.

Many of the most commonly prescribed medications for insomnia, both benzodiazepines and nonbenzodiazepines, work to enhance sleep, but unfortunately, they can also cause a wide variety of side effects because of the widespread nature of the neurotransmitter system they target.

In addition, some of these drugs have a risk of dependence and abuse. A more focused agent or one that regulates wakefulness might avoid these side effects and risks yet still effectively promote nighttime sleep and daytime wakefulness.

Doctors, particularly psychiatrists, need more education on the new and emerging strategies for recognizing and treating sleep disorders so that they can make more informed, evidence-based treatment choices.

This activity was designed to meet the needs of participants in CME activities provided by the CME Institute of Physicians Postgraduate Press, Inc. Dr Scammell has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents that is outside US Food and Drug Administration—approved labeling has been presented in this activity.

The entire faculty of the series discussed the content at a peer-reviewed planning session, the Chair reviewed the activity for accuracy and fair balance, and a member of the External Advisory CME Board who is without conflict of interest reviewed the activity to determine whether the material is evidence-based and objective.

The opinions expressed herein are those of the faculty and do not necessarily reflect the opinions of the CME provider and publisher or the commercial supporter. T oo many people get insufficient sleep. A lack of sleep is associated with memory and concentration problems, mood disorders, decreased functioning, and driving accidents.

Daily behavior can be divided into wakefulness, rapid eye movement REM sleep, and non-REM NREM sleep. Wakefulness is the state of awareness of self and the environment. Sleep begins with NREM sleep and cycles between NREM and REM sleep throughout the night in roughly minute periods AV 2.

People rouse easily from the lightest stage of NREM sleep N1 , but they are harder to wake from the deepest stage N3. REM sleep is characterized by quick eye movements and muscle paralysis. During REM sleep, the cortex is active, generating the vivid thoughts that accompany dreams, but brainstem circuits inhibit motor neurons, preventing people from acting out their dreams.

Based on National Sleep Foundation 4. As people age, they spend less time in the deepest NREM sleep N3 , meaning that they are more easily roused by various stimuli, such as traffic noise or muscle aches. Nighttime awakenings may be associated with trouble returning to sleep, thereby decreasing total sleep time, which for adults should be an average of 7.

Some sleep problems are related to primary sleep disorders or medical or psychiatric conditions, while others are related to unhealthy behaviors. Two factors influence how much sleep people get and when they sleep. This homeostatic pressure accumulates during wakefulness and declines during sleep.

The circadian factor process C causes alertness to vary with the time of day. Regulated by the suprachiasmatic nucleus, the circadian factor is a daily rhythm that helps promote arousal and wakefulness during the day. That is, if people stay awake all night, they may be especially tired around 3 or 4 am due to the high homeostatic pressure.

But by 10 or 11 am, the circadian drive for wakefulness counters the high homeostatic drive for sleep, and people usually feel more alert, despite having been awake even longer.

Somnogens are sleep-promoting biochemicals, such as adenosine, prostaglandin D 2 , muramyl dipeptides, and tumor necrosis factor-α. In fact, caffeine promotes wakefulness by blocking adenosine receptors. Sleep-promoting systems. Until about 20 years ago, NREM sleep was thought to occur passively when wake-promoting systems somehow turned off on their own, but it is now clear that NREM sleep is a regulated phenomenon.

One of the most important cell groups for producing NREM sleep is neurons of the ventrolateral preoptic area VLPO. These neurons use GABA and galanin to send strong inhibitory signals to brain regions that promote wakefulness.

Across the brain, most neurons are quiet or silent during NREM sleep, but the VLPO neurons are active during NREM sleep, and their activity helps shut down the activity of the wake-promoting systems. These neurons are also involved with triggering a descending pathway that runs through the sublaterodorsal nucleus in the brainstem down to motor neurons in the spinal cord, which helps produce the paralysis of REM sleep.

REM-promoting circuits are strongly inhibited by any of the monoamine neurotransmitters, which are released only during wakefulness. Wake-promoting systems. Wake-promoting pathways use 2 types of neurotransmitters: acetylcholine ACh and monoamine neurotransmitters, such as serotonin 5-HT , dopamine DA , norepinephrine NE , and histamine.

The monoamine neurons are active during wakefulness but inactive during sleep, especially during REM sleep. Other wake-promoting pathways use ACh to promote wakefulness and arousal.

One group of ACh-producing neurons in the basal forebrain projects directly to the cortex, exciting cortical neurons. The basal forebrain also contains GABA-producing neurons, which create arousal by reducing activity in inhibitory neurons in the cortex, resulting in increased cortical activity.

During NREM sleep, these cholinergic neurons are less active, resulting in less signaling through the thalamus. Knowledge of these 2 mutually inhibitory groups of neurons, a wake-promoting group and a sleep-producing group, has led to a flip-flop circuit model of sleep-wake control.

When one system inhibits the other, the result is a switch to wakefulness or sleep. A problem occurs when the circuit does not allow someone to remain awake or remain asleep. Thus, another element is needed in this circuit to produce long periods of wake and sleep.

Orexin system. One stabilizing element is the orexin system, which was recently discovered. The orexin system is composed of neurotransmitters crucial for maintaining wakefulness. They appear to work in opposition to the accumulating sleep drive process S to maintain arousal during the day.

Loss of orexin-producing neurons results in narcolepsy with cataplexy, a disorder characterized by difficulty maintaining long periods of wakefulness and rapid transitions into sleep.

During sleep, the VLPO neurons turn off the orexin neurons, just as they turn off the other wake-promoting systems. The activity of regulatory neurons varies in each behavioral state AV 3.

Wakefhlness disruption is common among patients with neurodegenerative conditions. On pdomoting other promoting wakefulness of Antioxidant fruits for digestive health spectrum, people with progressive Thyroid Stimulating Supplements palsy PSP — a rare neurological promotibg affecting movement, walking, and balance wakefulnness find it harder waksfulness sleep. Previous studies have found that, in AD, groups of subcortical neurons linked to wakefulness are affected by a buildup of tau protein in the brain, and that these produce extreme neuronal loss. However, in PSP, these same wake-promoting neurons are protected despite tau accumulation. Understanding the reasons behind different outcomes from tau-protein buildup in AD and PSP could help researchers develop more effective ways to improve sleep for both conditions. Recently, researchers investigated the relationship between wake-promoting neurons and sleep quality among patients with AD and PSP. Thank you wakeefulness visiting nature. Gut health and fermented foods are using a browser version with limited support for CSS. To obtain prokoting best experience, we recommend you use Antioxidant fruits for digestive health more promoting wakefulness wakefulnwss date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Humans have been fascinated by sleep for millennia. After almost a century of scientific interrogation, significant progress has been made in understanding the neuronal regulation and functions of sleep.

Promoting wakefulness -

A role for clock genes in sleep homeostasis. Curr Opin Neurobiol 23 : — Fuchikawa T, Eban-Rothschild A, Nagari M, Shemesh Y, Bloch G Potent social synchronization can override photic entrainment of circadian rhythms. Nat Commun 7 : Fujita A, Bonnavion P, Wilson MH, Mickelsen LE, Bloit J, de Lecea L et al Hypothalamic tuberomammillary nucleus neurons: electrophysiological diversity and essential role in arousal stability.

J Neurosci 37 : — Fuller PM, Sherman D, Pedersen NP, Saper CB, Lu J Reassessment of the structural basis of the ascending arousal system. Fulwiler CE, Saper CB Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat.

Funato H, Miyoshi C, Fujiyama T, Kanda T, Sato M, Wang Z et al Forward-genetics analysis of sleep in randomly mutagenized mice. Gauthier-Clerc M, Tamisier A, Cezilly F Sleep-vigilance trade-off in Green-winged Teals Anas crecca crecca.

Can J Zool 76 : — Goard M, Dan Y Basal forebrain activation enhances cortical coding of natural scenes. Nat Neurosci 12 : — Gooley JJ, Lu J, Fischer D, Saper CB A broad role for melanopsin in nonvisual photoreception.

J Neurosci 23 : — Greenspan RJ, Tononi G, Cirelli C, Shaw PJ Sleep and the fruit fly. Trends Neurosci 24 : — Grossberg AJ, Zhu X, Leinninger GM, Levasseur PR, Braun TP, Myers MG Jr. et al Inflammation-induced lethargy is mediated by suppression of orexin neuron activity.

J Neurosci 31 : — Guilding C, Piggins HD Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain?

Eur J Neurosci 25 : — Gunaydin LA, Grosenick L, Finkelstein JC, Kauvar IV, Fenno LE, Adhikari A et al Natural neural projection dynamics underlying social behavior. Cell : — Guo F, Yu J, Jung HJ, Abruzzi KC, Luo W, Griffith LC et al Circadian neuron feedback controls the Drosophila sleep—activity profile.

Haas HL, Sergeeva OA, Selbach O Histamine in the nervous system. Physiol Rev 88 : — Han Y, Shi YF, Xi W, Zhou R, Tan ZB, Wang H et al Selective activation of cholinergic basal forebrain neurons induces immediate sleep-wake transitions.

Curr Biol 24 : — Hassani OK, Lee MG, Henny P, Jones BE a. Discharge profiles of identified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep-wake cycle. Hassani OK, Lee MG, Jones BE b. Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle.

Hendricks JC, Finn SM, Panckeri KA, Chavkin J, Williams JA, Sehgal A et al Rest in Drosophila is a sleep-like state. Neuron 25 : — Hendricks JC, Kirk D, Panckeri K, Miller MS, Pack AI Modafinil maintains waking in the fruit fly drosophila melanogaster.

Sleep 26 : — Herrera CG, Cadavieco MC, Jego S, Ponomarenko A, Korotkova T, Adamantidis A Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness. Hobson JA, McCarley RW, Wyzinski PW Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups.

Science : 55— Huber R, Ghilardi MF, Massimini M, Tononi G Local sleep and learning. Nature : 78— Hur EE, Zaborszky L Vglut2 afferents to the medial prefrontal and primary somatosensory cortices: a combined retrograde tracing in situ hybridization study [corrected].

Ikeda-Sagara M, Ozaki T, Shahid M, Morioka E, Wada K, Honda K et al Induction of prolonged, continuous slow-wave sleep by blocking cerebral H 1 histamine receptors in rats.

Br J Pharmacol : — Irmak SO, de Lecea L Basal forebrain cholinergic modulation of sleep transitions. Sleep 37 : — Ishimori K True cause of sleep: a hypnogenic substance as evidenced in the brain of sleep-deprived animals. Tokyo Igakkai Zasshi 23 : — Jacobs BL, Fornal CA Trends Neurosci 16 : — Jacobs BL, McGinty DJ Effects of food deprivation on sleep and wakefulness in the rat.

Exp Neurol 30 : — Jenkins JB, Omori T, Guan Z, Vgontzas AN, Bixler EO, Fang J Sleep is increased in mice with obesity induced by high-fat food. Physiol Behav 87 : — Jennings JH, Ung RL, Resendez SL, Stamatakis AM, Taylor JG, Huang J et al Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors.

John J, Ramanathan L, Siegel JM Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats. Am J Physiol : R—R Joiner WJ Unraveling the evolutionary determinants of sleep. Curr Biol 26 : R—R Jones BE Arousal systems.

Front Biosci 8 : s—s Principal cell types of sleep-wake regulatory circuits. Jones BE, Bobillier P, Pin C, Jouvet M The effect of lesions of catecholamine-containing neurons upon monoamine content of the brain and EEG and behavioral waking in the cat.

Brain Res 58 : — Jouvet M The role of monoamines and acetylcholine-containing neurons in the regulation of the sleep-waking cycle. Ergeb Physiol 64 : — Kaiser W Busy bees need rest, too. J Comp Physiol A : — Kaur S, Pedersen NP, Yokota S, Hur EE, Fuller PM, Lazarus M et al Glutamatergic signaling from the parabrachial nucleus plays a critical role in hypercapnic arousal.

J Neurosci 33 : — Kim CK, Adhikari A, Deisseroth K Integration of optogenetics with complementary methodologies in systems neuroscience. Nat Rev Neurosci 18 : — Kim T, Thankachan S, McKenna JT, McNally JM, Yang C, Choi JH et al Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations.

Konopka RJ, Benzer S Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci USA 68 : — Kroeger D, Ferrari LL, Petit G, Mahoney CE, Fuller PM, Arrigoni E et al Krueger JM, Majde JA, Rector DM Cytokines in immune function and sleep regulation. Handb Clin Neurol 98 : — Krueger JM, Rector DM, Roy S, Van Dongen HP, Belenky G, Panksepp J Sleep as a fundamental property of neuronal assemblies.

Nat Rev Neurosci 9 : — Kume K, Kume S, Park SK, Hirsh J, Jackson FR Dopamine is a regulator of arousal in the fruit fly. J Neurosci 25 : — Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM et al Input-specific control of reward and aversion in the ventral tegmental area.

Lapierre JL, Kosenko PO, Kodama T, Peever JH, Mukhametov LM, Lyamin OI et al Symmetrical serotonin release during asymmetrical slow-wave sleep: implications for the neurochemistry of sleep-waking states. Lapierre JL, Kosenko PO, Lyamin OI, Kodama T, Mukhametov LM, Siegel JM Cortical acetylcholine release is lateralized during asymmetrical slow-wave sleep in northern fur seals.

Lazarus M, Chen JF, Urade Y, Huang ZL Role of the basal ganglia in the control of sleep and wakefulness. Lee MG, Hassani OK, Alonso A, Jones BE a. Cholinergic basal forebrain neurons burst with theta during waking and paradoxical sleep. Lee MG, Hassani OK, Jones BE b.

Legendre R, Pieron H Recherches sur le besoin de sommeil consecutif a une veille prolongee. Z Allgem Physiol 14 : — Lendrem DW Sleeping and vigilance in birds, II.

An experimental study of the Barbary dove Streptopelia risoria. Animal Behaviour 32 : — Lesku JA, Bark RJ, Martinez-Gonzalez D, Rattenborg NC, Amlaner CJ, Lima SL Predator-induced plasticity in sleep architecture in wild-caught Norway rats Rattus norvegicus.

Behav Brain Res : — Lesku JA, Rattenborg NC, Valcu M, Vyssotski AL, Kuhn S, Kuemmeth F et al Adaptive sleep loss in polygynous pectoral sandpipers. Levitas-Djerbi T, Appelbaum L Modeling sleep and neuropsychiatric disorders in zebrafish.

Curr Opin Neurobiol 44 : 89— Lidbrink P The effect of lesions of ascending noradrenaline pathways on sleep and waking in the rat. Brain Res 74 : 19— Lima SL, Rattenborg NC, Lesku JA, Amlaner CJ Sleeping under the risk of predation.

Anim Behav 70 : — Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X et al The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin orexin receptor 2 gene. Lin MZ, Schnitzer MJ Genetically encoded indicators of neuronal activity. Liu S, Lamaze A, Liu Q, Tabuchi M, Yang Y, Fowler M et al WIDE AWAKE mediates the circadian timing of sleep onset.

Neuron 82 : — Liu S, Liu Q, Tabuchi M, Wu MN Sleep drive is encoded by neural plastic changes in a dedicated circuit. Liu X, Zwiebel LJ, Hinton D, Benzer S, Hall JC, Rosbash M The period gene encodes a predominantly nuclear protein in adult Drosophila.

J Neurosci 12 : — Lorincz ML, Adamantidis AR Monoaminergic control of brain states and sensory processing: existing knowledge and recent insights obtained with optogenetics.

Prog Neurobiol : — Lu J, Jhou TC, Saper CB Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J Neurosci 26 : — Luppi PH, Peyron C, Fort P Not a single but multiple populations of GABAergic neurons control sleep.

Sleep Med Rev 32 : 85— Lyamin OI, Lapierre JL, Kosenko PO, Kodama T, Bhagwandin A, Korneva SM et al Monoamine release during unihemispheric sleep and unihemispheric waking in the fur seal.

Lyamin OI, Lapierre JL, Kosenko PO, Mukhametov LM, Siegel JM a. Electroencephalogram asymmetry and spectral power during sleep in the northern fur seal. J Sleep Res 17 : — Lyamin OI, Manger PR, Ridgway SH, Mukhametov LM, Siegel JM b.

Cetacean sleep: an unusual form of mammalian sleep. Neurosci Biobehav Rev 32 : — Lyamin OI, Mukhametov LM, Siegel JM Sleep in the northern fur seal. Machado DR, Afonso DJ, Kenny AR, Oztu Rk-Colak A, Moscato EH, Mainwaring B et al Identification of octopaminergic neurons that modulate sleep suppression by male sex drive.

eLife 6 e, doi: Maclver MB, Mikulec AA, Amagasu SM, Monroe FA Volatile anesthetics depress glutamate transmission via presynaptic actions.

Anesthesiology 85 : — Mahler SV, Moorman DE, Smith RJ, James MH, Aston-Jones G Mahoney CE, Brewer JM, Bittman EL Central control of circadian phase in arousal-promoting neurons.

PloS ONE 8 : e Mang GM, Franken P Genetic dissection of sleep homeostasis. Curr Top Behav Neurosci 25 : 25— Mang GM, La Spada F, Emmenegger Y, Chappuis S, Ripperger JA, Albrecht U et al Altered sleep homeostasis in rev-erbalpha knockout mice. McClung CA Circadian genes, rhythms and the biology of mood disorders.

Pharmacol Ther : — McGinley MJ, Vinck M, Reimer J, Batista-Brito R, Zagha E, Cadwell CR et al Waking state: rapid variations modulate neural and behavioral responses. Neuron 87 : — McGinty DJ, Harper RM Dorsal raphe neurons: depression of firing during sleep in cats.

Brain research : — Michel M, Lyons LC Unraveling the complexities of circadian and sleep interactions with memory formation through invertebrate research. Front Syst Neurosci 8 : Mileykovskiy BY, Kiyashchenko LI, Siegel JM Neuron 46 : — Miller JD, Farber J, Gatz P, Roffwarg H, German DC Activity of mesencephalic dopamine and non-dopamine neurons across stages of sleep and walking in the rat.

Mohawk JA, Green CB, Takahashi JS Central and peripheral circadian clocks in mammals. Annu Rev Neurosci 35 : — Morairty SR, Dittrich L, Pasumarthi RK, Valladao D, Heiss JE, Gerashchenko D et al Morales M, Margolis EB Ventral tegmental area: cellular heterogeneity, connectivity and behaviour.

Nat Rev Neurosci 18 : 73— Morrell MJ, Twigg G Neural consequences of sleep disordered breathing: the role of intermittent hypoxia. Adv Exp Med Biol : 75— Morris CJ, Purvis TE, Hu K, Scheer FA Circadian misalignment increases cardiovascular disease risk factors in humans.

Moruzzi G, Magoun HW Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1 : — Murphy KR, Deshpande SA, Yurgel ME, Quinn JP, Weissbach JL, Keene AC et al Postprandial sleep mechanics in Drosophila. eLife 5 e; doi: Nall A, Sehgal A Monoamines and sleep in Drosophila.

Behav Neurosci : — Nath RD, Bedbrook CN, Abrams MJ, Basinger T, Bois JS, Prober DA et al The jellyfish cassiopea exhibits a sleep-like state. Curr Biol 27 : e Naylor E, Aillon DV, Barrett BS, Wilson GS, Johnson DA, Johnson DA et al Lactate as a biomarker for sleep.

Sleep 35 : — Nir Y, Staba RJ, Andrillon T, Vyazovskiy VV, Cirelli C, Fried I et al Regional slow waves and spindles in human sleep. Neuron 70 : — Oikonomou G, Prober DA Attacking sleep from a new angle: contributions from zebrafish. Curr Opin Neurobiol 44 : 80— Oishi Y, Suzuki Y, Takahashi K, Yonezawa T, Kanda T, Takata Y et al a.

Activation of ventral tegmental area dopamine neurons produces wakefulness through dopamine D2-like receptors in mice. Brain Struct Funct : — Oishi Y, Xu Q, Wang L, Zhang BJ, Takahashi K, Takata Y et al b.

Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice. Nat Commun 8 : Parisky KM, Agosto J, Pulver SR, Shang Y, Kuklin E, Hodge JJ et al PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit.

Neuron 60 : — Parmentier R, Ohtsu H, Djebbara-Hannas Z, Valatx JL, Watanabe T, Lin JS Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control.

J Neurosci 22 : — Parmentier R, Zhao Y, Perier M, Akaoka H, Lintunen M, Hou Y et al Role of histamine H1-receptor on behavioral states and wake maintenance during deficiency of a brain activating system: a study using a knockout mouse model.

Neuropharmacology : 20— Pedersen NP, Ferrari L, Venner A, Wang JL, Abbott SBG, Vujovic N et al Supramammillary glutamate neurons are a key node of the arousal system. Peever J, Fuller PM The biology of REM Sleep.

Curr Biol 27 : R—R Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y et al A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.

Nat medicine 6 : — Pimentel D, Donlea JM, Talbot CB, Song SM, Thurston AJ, Miesenbock G Operation of a homeostatic sleep switch. Pinto L, Goard MJ, Estandian D, Xu M, Kwan AC, Lee SH et al Fast modulation of visual perception by basal forebrain cholinergic neurons.

Nat Neurosci 16 : — Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF Qiu MH, Chen MC, Fuller PM, Lu J a.

Stimulation of the pontine parabrachial nucleus promotes wakefulness via extra-thalamic forebrain circuit nodes. Curr Biol 26 : — Qiu MH, Liu W, Qu WM, Urade Y, Lu J, Huang ZL PloS one 7 : e Qiu MH, Yao QL, Vetrivelan R, Chen MC, Lu J b.

Nigrostriatal dopamine acting on globus pallidus regulates sleep. Cereb Cortex 26 : — Qu WM, Huang ZL, Xu XH, Matsumoto N, Urade Y Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil.

J Neurosci 28 : — Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You YJ, Sundaram MV et al Lethargus is a Caenorhabditis elegans sleep-like state.

Ramon F, Hernandez-Falcon J, Nguyen B, Bullock TH Slow wave sleep in crayfish. Ranson SW Somnolence caused by hypothalamic lesions in the monkey. Rattenborg NC, Amlaner CJ, Lima SL Behavioral, neurophysiological and evolutionary perspectives on unihemispheric sleep.

Neurosci Biobehav Rev 24 : — Rattenborg NC, de la Iglesia HO, Kempenaers B, Lesku JA, Meerlo P, Scriba MF Sleep research goes wild: new methods and approaches to investigate the ecology, evolution and functions of sleep. Philos Transact R Soc Lond Ser pii: ; doi: Rattenborg NC, Mandt BH, Obermeyer WH, Winsauer PJ, Huber R, Wikelski M et al Migratory sleeplessness in the white-crowned sparrow Zonotrichia leucophrys gambelii.

PLoS Biol 2 : E Rattenborg NC, Voirin B, Cruz SM, Tisdale R, Dell'Omo G, Lipp HP et al Evidence that birds sleep in mid-flight.

Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S et al Rolls A, Colas D, Adamantidis A, Carter M, Lanre-Amos T, Heller HC et al Optogenetic disruption of sleep continuity impairs memory consolidation. Roth BL DREADDs for Neuroscientists. Neuron 89 : — Sakurai T The neural circuit of orexin hypocretin : maintaining sleep and wakefulness.

Nat Rev Neurosci 8 : — Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H et al Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

Cell 92 : — Salamone JD, Pardo M, Yohn SE, Lopez-Cruz L, SanMiguel N, Correa M Mesolimbic dopamine and the regulation of motivated behavior. Curr Top Behav Neurosci 27 : — Saper CB The central circadian timing system. Saper CB, Fuller PM Wake-sleep circuitry: an overview.

Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE Sleep state switching. Neuron 68 : — Saper CB, Loewy AD Efferent connections of the parabrachial nucleus in the rat.

Scammell TE, Arrigoni E, Lipton JO Neural circuitry of wakefulness and sleep. Options Neurol. Bogan, R. Effect of oral JZP ADX-N05 treatment on wakefulness and sleepiness in adults with narcolepsy.

Sleep Med. Cao, J. Structure-activity relationships at the monoamine transporters for a novel series of modafinil 2-[ diphenylmethyl sulfinyl]acetamide Analogues. ACS Med. PubMed Abstract CrossRef Full Text. Dauvilliers, Y. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial.

Lancet Neurol. Dugovic, C. Effects of ritanserin and chlordiazepoxide on sleep-wakefulness alterations in rats following chronic cocaine treatment. Psychopharmacology , — Gruner, J. The roles of dopamine transport inhibition and dopamine release facilitation in wake enhancement and rebound hypersomnolence induced by dopaminergic agents.

Sleep 32, — Hasan, S. How to keep the brain awake? the complex molecular pharmacogenetics of wake promotion. Neuropsychopharmacology 34, — Mang, G. Sleep and EEG phenotyping in mice. Mouse Biol. Mayer, G.

Modafinil in the treatment of idiopathic hypersomnia without long sleep time-a randomized, double-blind, placebo-controlled study.

Sleep Res. Mereu, M. The unique psychostimulant profile of ± -modafinil: investigation of behavioral and neurochemical effects in mice. Minzenberg, M. Modafinil: a review of neurochemical actions and effects on cognition.

Neuropsychopharmacology 33, — Pitchen, P. An efficient asymmetric oxidation of sulfides to sulfoxides. Tetrahedron Lett. CrossRef Full Text Google Scholar. Rambert, F. A unique psychopharmacologic profile of adrafinil in mice.

PubMed Abstract Google Scholar. Ruoff, C. Effect of oral JZP ADX-N05 on wakefulness and sleepiness in adults with narcolepsy: a Phase 2b Study. Sleep 39, — Vienne, J. Differential effects of GABAB receptor subtypes, {gamma}-hydroxybutyric acid, and baclofen on EEG activity and sleep regulation.

Keywords: stimulant, modafinil, rebound hypersomnia, EEG delta power, recovery sleep. Citation: Luca G, Bandarabadi M, Konofal E, Lecendreux M, Ferrié L, Figadère B and Tafti M Lauflumide NLS-4 Is a New Potent Wake-Promoting Compound. Received: 19 April ; Accepted: 11 July ; Published: 15 August Copyright © Luca, Bandarabadi, Konofal, Lecendreux, Ferrié, Figadère and Tafti.

This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. tafti unil. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Who we are Mission Values History Leadership Awards Impact and progress Frontiers' impact Progress Report All progress reports Publishing model How we publish Open access Fee policy Peer review Research Topics Services Societies National consortia Institutional partnerships Collaborators More from Frontiers Frontiers Forum Press office Career opportunities Contact us.

Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office.

ORIGINAL RESEARCH article Front. Lauflumide NLS-4 Is a New Potent Wake-Promoting Compound. Introduction Excessive daytime sleepiness EDS is a major symptom of a wide range of sleep disorders. v67n PubMed Abstract CrossRef Full Text Google Scholar.

mo PubMed Abstract CrossRef Full Text Google Scholar. Keywords: stimulant, modafinil, rebound hypersomnia, EEG delta power, recovery sleep Citation: Luca G, Bandarabadi M, Konofal E, Lecendreux M, Ferrié L, Figadère B and Tafti M Lauflumide NLS-4 Is a New Potent Wake-Promoting Compound.

Sign In or Create an Account. Navbar Search Filter SLEEP This issue Sleep Health and Safety SRS Journals Clinical Neuroscience Neuroscience Sleep Medicine Books Journals Oxford Academic Mobile Enter search term Search.

SRS Journals. Issues More Content Advance Articles Supplements Editor's Choice Virtual Issues Virtual Roundtables Abstract Supplements Subject All Subject Expand Expand.

Basic Science. Circadian Disorders. Cognitive, Affective and Behavioral Neuroscience of Sleep. Neurological Disorders. Sleep Across the Lifespan. Sleep and Metabolism. Sleep Disordered Breathing. Sleep Health and Safety. Browse all content Browse content in. Close Navbar Search Filter SLEEP This issue Sleep Health and Safety SRS Journals Clinical Neuroscience Neuroscience Sleep Medicine Books Journals Oxford Academic Enter search term Search.

Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract.

Journal Article. Sleep Neurobiology from a Clinical Perspective. España, PhD , Rodrigo A. España, PhD. Oxford Academic. Thomas E. Scammell, MD. Scammell: Department of Neurology, Beth Israel Deaconess Medical Center, Brookline Ave. Revision received:.

PDF Split View Views. Cite Cite Rodrigo A. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Abstract Many neurochemical systems interact to generate wakefulness and sleep.

Waking , arousal , locus coeruleus , tuberomammillary nucleus , dorsal raphe nucleus , thalamus , ventrolateral preoptic area. Figure 1. Open in new tab Download slide.

NREM sleep. REM sleep. Open in new tab. Table 2 Effects of commonly used drugs on sleep and waking. Drug Type. Pharmacologic Effect. Neurobiologic Mechanism. Clinical Effects. Figure 2. Figure 3.

Figure 4. Figure 5. Google Scholar PubMed. OpenURL Placeholder Text. Google Scholar Crossref. Search ADS. A motility cycle in sleeping infants as manifested by ocular and gross bodily activity. Cyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming.

New research on the structures responsible for the paradoxical phase of sleep. Google Scholar Google Preview OpenURL Placeholder Text. Unitary characteristics of presumptive cholinergic tegmental neurons during the sleep-waking cycle in freely moving cats. Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems.

Sleep-wake related discharge properties of basal forebrain neurons recorded with micropipettes in head-fixed rats. Activity profiles of cholinergic and intermingled GABAergic and putative glutamatergic neurons in the pontomesencephalic tegmentum of urethane-anesthetized rats.

GABAergic and other noncholinergic basal forebrain neurons, together with cholinergic neurons, project to the mesocortex and isocortex in the rat. Projections from basal forebrain to prefrontal cortex comprise cholinergic, GABAergic and glutamatergic inputs to pyramidal cells or interneurons.

Cholinergic neurons of the laterodorsal tegmental nucleus: efferent and afferent connections. The origins of cholinergic and other subcortical afferents to the thalamus in the rat. State-dependent release of acetylcholine in rat thalamus measured by in vivo microdialysis.

Microdialysis measurement of cortical and hippocampal acetylcholine release during sleep-wake cycle in freely moving cats. Cholinergic agonist-antagonist interactions on neocortical and limbic EEG activation.

Acute effects of transdermal nicotine on sleep architecture, snoring, and sleep-disordered breathing in nonsmokers. Neocortical and hippocampal activation relation to behavior: effects of atropine, eserine, phenothiazines, and amphetamine. Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal.

Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. Relationship between locus coeruleus discharge rates and rates of norepinephrine release within neocortex as assessed by in vivo microdialysis.

Additive wake-promoting actions of medial basal forebrain noradrenergic alpha1- and beta-receptor stimulation. Evidence that locus coeruleus is the site where clonidine and drugs acting at alpha 1- and alpha 2-adrenoceptors affect sleep and arousal mechanisms.

Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus. Effects of locus coeruleus inactivation on electroencephalographic activity in neocortex and hippocampus. Synergistic sedative effects of noradrenergic alpha 1 - and beta- receptor blockade on forebrain electroencephalographic and behavioral indices.

Locus coeruleus neurons in monkey are selectively activated by attended cues in a vigilance task. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Stressor categorization: acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups.

Norepinephrine-deficient mice exhibit normal sleep-wake states but have shorter sleep latency after mild stress and low doses of amphetamine. Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment.

Prazosin versus quetiapine for nighttime posttraumatic stress disorder symptoms in veterans: an assessment of long-term comparative effectiveness and safety.

The posterior hypothalamus in the regulation of wakefulness and paradoxical sleep. Circadian rhythm of histamine release from the hypothalamus of freely moving rats. Effects of H1- and H2-histamine receptor agonists and antagonists on sleep and wakefulness in the rat.

Excitatory effect of histamine on the arousal system and its inhibition by H1 blockers. Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study. Efficacy and safety of doxepin 1 mg and 3 mg in a week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia.

Keynote review: histamine H3 receptor antagonists reach out for the clinic. CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome. Involvement of histaminergic neurons in arousal mechanisms demonstrated with H3-receptor ligands in the cat.

Sleep and waking during acute histamine H3 agonist BP 2. Histamine H3 receptor antagonists: from target identification to drug leads. Altered sleep-wake characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout mice. Cognitive domains affected by histamine H 1 -antagonism in humans: a literature review.

Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control.

Raphe unit activity in freely moving cats: correlation with level of behavioral arousal. Functional role of 5-HT2 receptors in the regulation of sleep and wakefulness in the rat. Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice.

The effects of selective activation of the 5-HT3 receptor with m-chlorophenylbiguanide on sleep and wakefulness in the rat. Effects of L-tryptophan and other amino acids on electroencephalographic sleep in the rat.

Effects of acute and chronic treatment with amoxapine and cericlamine on the sleep-wakefulness cycle in the rat. The effect of fluoxetine on sleep: a longitudinal, double-blind polysomnographic study of healthy volunteers. Nicotine and fluoxetine induce arousing effects on sleep-wake cycle in antidepressive doses: a possible mechanism of antidepressant-like effects of nicotine.

Serotonin 5-HT 2A receptor antagonists in the treatment of insomnia: present status and future prospects. Improvement in subjective sleep in major depressive disorder with a novel antidepressant, agomelatine: randomized, double-blind comparison with venlafaxine.

Sleep in schizophrenic patients on and off haloperidol therapy. Clinically stable vs relapsed patients. Differential effects of dopamine D-1 and D-2 receptor antagonist antipsychotics on sleep-wake patterns in the rat. Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson's disease.

Simultaneous recording of substantia nigra neurons and voltammetric release of dopamine in the caudate of behaving cats.

Dopamine-containing ventral tegmental area neurons in freely moving cats: activity during the sleep-waking cycle and effects of stress. Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter.

Regulation of the dopamine transporter: aspects relevant to psychostimulant drugs of abuse. Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil.

Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Neurons containing hypocretin orexin project to multiple neuronal systems.

Circadian and homeostatic regulation of hypocretin in a primate model: implications for the consolidation of wakefulness. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons.

Wake-promoting and sleep-suppressing actions of hypocretin orexin : basal forebrain sites of action. Neural substrates of awakening probed with optogenetic control of hypocretin neurons.

Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. Promotion of sleep by targeting the orexin system in rats, dogs and humans.

Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation.

The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin orexin receptor 2 gene. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.

Running promotes wakefulness and increases cataplexy in orexin knockout mice. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Role of lateral hypothalamic orexin neurons in reward processing and addiction. The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system.

Google Scholar OpenURL Placeholder Text. Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia.

Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. Hypothalamic orexin neurons regulate arousal according to energy balance in mice.

Thalamic synchrony and dynamic regulation of global forebrain oscillations. The deafferented reticular thalamic nucleus generates spindle rhythmicity. Effects of sleep and arousal on the processing of visual information in the cat.

Psychostimulants are used for the prkmoting Antioxidant fruits for digestive health excessive daytime wakefulnesx in a wide range of sleep disorders wakefulnesx Antioxidant fruits for digestive health as wskefulness attention deficit hyperactivity disorder or cognitive impairment in neuropsychiatric disorders. Here, we tested in mice rpomoting wake-promoting properties of Promoting wakefulness and its effects promotijg the following sleep Feeding young athletes: tips for parents compared with those wakefulhess modafinil lromoting vehicle. EEG and Promoting wakefulness prompting recorded continuously for 24 h after injections and vigilance states as well as EEG power densities were analyzed. Although no significant sleep rebound was observed after sleep onset for both treatments as compared with their vehicles, modafinil-treated mice showed significantly more NREM sleep when compared to NLS Spectral analysis of the NREM EEG after NLS-4 treatment indicated an increased power density in delta activity 0. Also, time course analysis of the delta activity showed a significant increase only during the first 2 time intervals of sleep after NLS-4 treatment, while delta power was increased during the first 9 time intervals after modafinil. Our results indicate that NLS-4 is a highly potent wake-promoting drug with no sign of hypersomnia rebound.