The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway
Abstract
We investigated the role of regionally discrete GABA (gamma-aminobutyric acid) receptors in the sedative response to pharmacological agents that act on GABA(A) receptors (muscimol, propofol and pentobarbital; 'GABAergic agents') and to ketamine, a general anesthetic that does not affect GABA(A) receptors. Behavioral studies in rats showed that the sedative response to centrally administered GABAergic agents was attenuated by the GABA(A) receptor antagonist gabazine (systemically administered). The sedative response to ketamine, by contrast, was unaffected by gabazine. Using c-Fos as a marker of neuronal activation, we identified a possible role for the tuberomammillary nucleus (TMN): when gabazine was microinjected directly into the TMN, it attenuated the sedative response to GABAergic agents. Furthermore, the GABA(A) receptor agonist muscimol produced a dose-dependent sedation when it was administered into the TMN. We conclude that the TMN is a discrete neural locus that has a key role in the sedative response to GABAergic anesthetics.
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The shared circuits hypothesis between sleep and anesthesia has been replicated across invertebrates to mammals.
“This shared circuits hypothesis has been replicated across divergent species spanning invertebrates to mammals [54, 58, 82, 98, 99, 101].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [98]
Except for ketamine, systemic hypnotic doses of every general anesthetic examined recruit sleep-promoting VLPO neurons.
“with the exception of ketamine, systemic delivery of hypnotic doses of every general anesthetic examined recruits sleep-promoting neurons in the VLPO [98–102]”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [98]
VLPO metabolic activation, measured by c-Fos, is associated with various sedative-hypnotic drugs.
“identified the metabolic activation of VLPO—as determined by c-Fos expression, a marker of antecedent cellular activity—in association with a variety of sedative-hypnotic drugs [98–100].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [98]
Using c-Fos as a proxy, neurons in many wake-promoting nuclei are inhibited during general anesthesia.
“using c-Fos as a proxy for antecedent activity, neurons within many of these nuclei have been identified to be inhibited during general anesthesia [98, 100, 101, 114].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [98]
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Molecular and cellular mechanisms of general anaesthesia
Franks, N. P., & Lieb, W. R. (1994) · Nature · doi:10.1038/367607a0 · Cited by 1,786 · see citing works
Self-citationAnis, N. A., Berry, S. C., Burton, N. R., & Lodge, D. (1983) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1983.tb11031.x · Cited by 1,399 · see citing works
Activation of ventrolateral preoptic neurons during sleep
Sherin, J. E., Shiromani, P. J., McCarley, R. W., & Saper, C. B. (1996) · Science · doi:10.1126/science.271.5246.216 · Cited by 1,111 · see citing works
Self-citationSherin, J. E., Elmquist, J. K., Torrealba, F., & Saper, C. B. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04705.1998 · Cited by 746 · see citing works
Self-citationc-Fos and Related Immediate Early Gene Products as Markers of Activity in Neuroendocrine Systems
Hoffman, G. E., Smith, M. S., & Verbalis, J. G. (1993) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1993.1006 · Cited by 715 · see citing works
Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin
Jevtović‐Todorović, V., Todorovć, S. M., Mennerick, S. J., Powell, S., Dikranian, K. T., Benshoff, N. D., Zorumski, C. F., & Olney, J. W. (1998) · Nature Medicine · doi:10.1038/nm0498-460 · Cited by 675 · see citing works
How does xenon produce anaesthesia?
Franks, N. P., Dickinson, R., de Sousa, S. L. M., Hall, A. C., & Lieb, W. R. (1998) · Nature · doi:10.1038/24525 · Cited by 514 · see citing works
Self-citationIdentification of sleep-promoting neurons in vitro
Gallopin, T., Fort, P., Eggermann, E., Cauli, B., Luppi, P.-H., Rossier, J., Audinat, E., Mühlethaler, M., & Serafin, M. (2000) · Nature · doi:10.1038/35010109 · Cited by 504 · see citing works
Afferents to the Ventrolateral Preoptic Nucleus
Chou, T. C., Bjørkum, A. A., Gaus, S. E., Lu, J., Scammell, T. E., & Saper, C. B. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00977.2002 · Cited by 493 · see citing works
Self-citationFiset, P., Paus, T., Daloze, T., Plourde, G., Meuret, P., Bonhomme, V., Hajj-Ali, N., Backman, S. B., & Evans, A. C. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-13-05506.1999 · Cited by 475 · see citing works
A Hypnotic Response to Dexmedetomidine, an α2 Agonist, Is Mediated in the Locus Coerüleus in Rats
Corréa-Sales, C., Rabin, B. C., & Maze, M. (1992) · Anesthesiology · doi:10.1097/00000542-199206000-00013 · Cited by 403 · see citing works
Self-citationGeneral anaesthetic actions on ligand-gated ion channels
Krasowski, M. D., & Harrison, N. L. (1999) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s000180050371 · Cited by 384 · see citing works
Hales, T. G., & Lambert, J. J. (1991) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1991.tb12479.x · Cited by 356 · see citing works
Cerebral Metabolism during Propofol Anesthesia in Humans Studied with Positron Emission Tomography
Alkire, M. T., Haier, R. J., Barker, S. J., Shah, N. K., Wu, J. C., & Kao, J. Y. (1995) · Anesthesiology · doi:10.1097/00000542-199502000-00010 · Cited by 350 · see citing works
The Role of the GABAA Receptor/Chloride Channel Complex in Anesthesia
Tanelian, D. L., Kosek, P. S., Módy, I., & MacIver, M. B. (1993) · Anesthesiology · doi:10.1097/00000542-199304000-00020 · Cited by 349 · see citing works
Elmquist, J. K., Scammell, T. E., Jacobson, C. D., & Saper, C. B. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960715)371:1 · Cited by 335 · see citing works
Self-citationEvidence for histaminergic arousal mechanisms in the hypothalamus of cat
Lin, J., Sakai, K., & Jouvet, M. (1988) · Neuropharmacology · doi:10.1016/0028-3908(88)90159-1 · Cited by 330 · see citing works
Stell, B. M., & Módy, I. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-10-j0003.2002 · Cited by 328 · see citing works
Organization of cerebral cortical afferent systems in the rat. II. Hypothalamocortical projections
Saper, C. B. (1985) · The Journal of Comparative Neurology · doi:10.1002/cne.902370103 · Cited by 324 · see citing works
Self-citationSleep–waking discharge of neurons in the posterior lateral hypothalamus of the albino rat
Steininger, T. L., Alam, M. N., Gong, H., Szymusiak, R. S., & McGinty, D. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01648-0 · Cited by 257 · see citing works
ON BIOLOGICAL ASSAYS INVOLVING QUANTAL RESPONSES
Waud, D. R. (1972) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29374-0 · Cited by 247 · see citing works
Steininger, T. L., Gong, H., McGinty, D., & Szymusiak, R. S. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20010122)429:4 · Cited by 240 · see citing works
Lin, J., Hou, Y., Sakai, K., & Jouvet, M. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-04-01523.1996 · Cited by 234 · see citing works
Hara, M., Kai, Y., & Ikemoto, Y. (1993) · Anesthesiology · doi:10.1097/00000542-199310000-00021 · Cited by 215 · see citing works
Devor, M. G., & Zalkind, V. I. (2001) · Pain · doi:10.1016/s0304-3959(01)00345-1 · Cited by 176 · see citing works
Involvement of histamine in the control of the waking state
Monti, J. M. (1993) · Life Sciences · doi:10.1016/0024-3205(93)90592-q · Cited by 162 · see citing works
GABA release in posterior hypothalamus across sleep-wake cycle
Nitz, D. A., & Siegel, J. M. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.271.6.r1707 · Cited by 150 · see citing works
Inhibitory post‐synaptic currents in rat hippocampal CA1 neurones.
Collingridge, G. L., Gage, P. W., & Robertson, B. (1984) · The Journal of Physiology · doi:10.1113/jphysiol.1984.sp015482 · Cited by 150 · see citing works
On the Functional Significance of c-fos Induction During the Sleep-waking Cycle
Cirelli, C., & Tononi, G. (2000) · SLEEP · doi:10.1093/sleep/23.4.9 · Cited by 139 · see citing works
Sawamura, S., Kingery, W. S., Davies, M. F., Agashe, G. S., Clark, J. D., Kobilka, B. K., Hashimoto, T., & Maze, M. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09242.2000 · Cited by 135 · see citing works
Self-citationGeneral anaesthetic action at transmitter-gated inhibitory amino acid receptors
Belelli, D., Pistis, M., Peters, J. A., & Lambert, J. J. (1999) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(99)01405-4 · Cited by 132 · see citing works
Multiple neurotransmitters in the tuberomammillary nucleus: Comparison of rat, mouse, and guinea pig
Airaksinen, M. S., Alanen, S., Szabat, E., Visser, T. J., & Panula, P. (1992) · The Journal of Comparative Neurology · doi:10.1002/cne.903230109 · Cited by 130 · see citing works
Pentobarbital: Selective Depression of Excitatory Postsynaptic Potentials
Barker, J. L., & Gainer, H. (1973) · Science · doi:10.1126/science.182.4113.720 · Cited by 114 · see citing works
Adodra, S., & Hales, T. G. (1995) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1995.tb15903.x · Cited by 95 · see citing works
Villar, M. J., Meister, B., Cortés, R., Schalling, M., Morris, M., & Hökfelt, T. G. M. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90361-7 · Cited by 76 · see citing works
GABA‐like immunoreactivity in the tuberomammillary nucleus: An electron microscopic study in the rat
Ericson, H., Köhler, C., & Blomqvist, A. G. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903050309 · Cited by 58 · see citing works
Lam, D. W., & Reynolds, J. N. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01334-6 · Cited by 56 · see citing works
Molecular Determinants of General Anesthetic Action: Role of GABAA Receptor Structure
Lin, L., Whiting, P. J., & HARRIS, R. A. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03320.x · Cited by 50 · see citing works
Depczynski, B., Nichol, K. A., FAITHI, Z., Iismaa, T. P., Shine, J., & Cunningham, A. M. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb10689.x · Cited by 48 · see citing works
c-Fos expression during wakefulness and sleep
Pompeiano, M., Cirelli, C., Arrighi, P., & Tononi, G. (1995) · Neurophysiologie Clinique · doi:10.1016/0987-7053(96)84906-9 · Cited by 48 · see citing works
Augmentation of GABA-induced current in frog sensory neurons by pentobarbital
Akaike, N., Tokutomi, N., & Ikemoto, Y. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.258.3.c452 · Cited by 45 · see citing works
Fos-like immunoreactivity in the rat brain in spontaneous wakefulness and sleep.
Cirelli, C., Pompeiano, M., & Tononi, G. (1993) · PubMed · Cited by 36 · see citing works
Inducing Anesthesia with a GABA Analog, THIP
Cheng, S., & Brunner, E. A. (1985) · Anesthesiology · doi:10.1097/00000542-198508000-00005 · Cited by 34 · see citing works
Effects of pentobarbitone on acetylcholine‐activated channels in mammalian muscle
Gage, P. W., & McKinnon, D. H. (1985) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1985.tb08851.x · Cited by 29 · see citing works
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Pandharipande, P. P., Pun, B. T., Herr, D., Maze, M., Girard, T. D., Miller, R. R., Shintani, A., Thompson, J. L., Jackson, J. C., Deppen, S. A., et al. (2007) · JAMA · doi:10.1001/jama.298.22.2644 · Cited by 1,456 · see citing works
Self-citationGeneral Anesthesia, Sleep, and Coma
Brown, E. N., Lydic, R., & Schiff, N. D. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0808281 · Cited by 1,346 · see citing works
General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
Franks, N. P. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2372 · Cited by 1,266 · see citing works
Self-citationHistamine in the Nervous System
Haas, H. L., Sergeeva, O. A., & Selbach, O. (2008) · Physiological Reviews · doi:10.1152/physrev.00043.2007 · Cited by 1,227 · see citing works
The role of histamine and the tuberomamillary nucleus in the nervous system
Haas, H. L., & Panula, P. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1034 · Cited by 914 · see citing works
Clinical Electroencephalography for Anesthesiologists
Purdon, P. L., Sampson, A. L., Pavone, K. J., & Brown, E. N. (2015) · Anesthesiology · doi:10.1097/aln.0000000000000841 · Cited by 869 · see citing works
Mechanisms of Actions of Inhaled Anesthetics
Campagna, J. A., Miller, K. W., & Forman, S. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmra021261 · Cited by 805 · see citing works
Molecular and neuronal substrates for general anaesthetics
Rudolph, U., & Antkowiak, B. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1496 · Cited by 771 · see citing works
Samuels, E., & Szabadi, E. (2008) · Current Neuropharmacology · doi:10.2174/157015908785777229 · Cited by 766 · see citing works
Boveroux, P., Vanhaudenhuyse, A., Bruno, M.-A., Noirhomme, Q., Lauwick, S., Luxen, A., Degueldre, C., Plenevaux, A., Schnakers, C., Phillips, C., et al. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181f697f5 · Cited by 630 · see citing works
Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness
Ferrarelli, F., Massimini, M., Sarasso, S., Casali, A., Riedner, B. A., Angelini, G., Tononi, G., & Pearce, R. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913008107 · Cited by 554 · see citing works
General Anesthesia and Altered States of Arousal: A Systems Neuroscience Analysis
Brown, E. N., Purdon, P. L., & Dort, C. J. V. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153200 · Cited by 551 · see citing works
Emerging molecular mechanisms of general anesthetic action
Hemmings, H. C., Akabas, M. H., Goldstein, P. A., Trudell, J. R., Orser, B. A., & Harrison, N. L. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.08.006 · Cited by 542 · see citing works
Vogt, B. A., & Laureys, S. (2005) · Progress in brain research · doi:10.1016/s0079-6123(05)50015-3 · Cited by 497 · see citing works
Unresponsiveness ≠ unconsciousness
Sanders, R. D., Tononi, G., Laureys, S., Sleigh, J. W., & Warner, D. S. (2012) · Anesthesiology · doi:10.1097/aln.0b013e318249d0a7 · Cited by 474 · see citing works
Circuits and functions of the lateral habenula in health and in disease
Hu, H., Cui, Y., & Yang, Y. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0292-4 · Cited by 471 · see citing works
Samuels, E., & Szabadi, E. (2008) · Current Neuropharmacology · doi:10.2174/157015908785777193 · Cited by 454 · see citing works
Dexmedetomidine Attenuates Isoflurane-induced Neurocognitive Impairment in Neonatal Rats
Sanders, R. D., Xu, J., Shu, Y., Januszewski, A. P., Halder, S., Fidalgo, A. R., Sun, P., Hossain, M., Ma, D., & Maze, M. (2009) · Anesthesiology · doi:10.1097/aln.0b013e31819daedd · Cited by 429 · see citing works
Self-citationMolecular targets underlying general anaesthesia
Franks, N. P. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706441 · Cited by 376 · see citing works
Self-citationA genetically encoded fluorescent sensor for in vivo imaging of GABA
Marvin, J. S., Shimoda, Y., Magloire, V., Leite, M., Kawashima, T., Jensen, T. P., Kolb, I., Knott, E. L., Novák, O., Podgorski, K., et al. (2019) · Nature Methods · doi:10.1038/s41592-019-0471-2 · Cited by 350 · see citing works
An essential role for orexins in emergence from general anesthesia
Kelz, M. B., Sun, Y., Chen, J., Cheng Meng, Q., Moore, J. T., Veasey, S. C., Dixon, S., Thornton, M., Funato, H., & Yanagisawa, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707146105 · Cited by 341 · see citing works
Cyclic and Sleep-Like Spontaneous Alternations of Brain State Under Urethane Anaesthesia
Clement, E., Richard, A., Thwaites, M., Ailon, J., Peters, S. R., & Dickson, C. T. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002004 · Cited by 337 · see citing works
Functional neuroanatomy of the central noradrenergic system
Szabadi, E. (2013) · Journal of Psychopharmacology · doi:10.1177/0269881113490326 · Cited by 337 · see citing works
Sedation and Anesthesia Mediated by Distinct GABA <sub>A</sub> Receptor Isoforms
Reynolds, D. S., Rosahl, T. W., Cirone, J., O'Meara, G. F., Haythornthwaite, A., Newman, R. J., Myers, J., Sur, C., Howell, O., Rutter, A. R., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-24-08608.2003 · Cited by 318 · see citing works
General anesthesia selectively disrupts astrocyte calcium signaling in the awake mouse cortex
Thrane, A. S., Thrane, V. R., Zeppenfeld, D. M., Lou, N., Xu, Q., Nagelhus, E. A., & Nedergaard, M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209448109 · Cited by 309 · see citing works
Awareness and recall during general anesthesia
Chung, H. S. (2014) · Korean Journal of Anesthesiology · doi:10.4097/kjae.2014.66.5.339 · Cited by 299 · see citing works
Oscillating circuitries in the sleeping brain
Adamantidis, A. R., Gutierrez Herrera, C., & Gent, T. C. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0223-4 · Cited by 281 · see citing works
Neuronal Machinery of Sleep Homeostasis in Drosophila
Donlea, J. M., Pimentel, D. O., & Miesenböck, G. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.013 · Cited by 269 · see citing works
Arnold, A. J., Razavieh, A., Nasr, J. R., Schulman, D. S., Eichfeld, C. M., & Das, S. (2017) · ACS Nano · doi:10.1021/acsnano.7b00113 · Cited by 264 · see citing works
Genesis of sleep bruxism: Motor and autonomic-cardiac interactions
Lavigne, G. J., Huynh, N. T., Kato, T., Okura, K., Adachi, K., Yao, D., & Sessle, B. J. (2007) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2006.11.017 · Cited by 261 · see citing works
Histamine in the regulation of wakefulness
Thakkar, M. M. (2011) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2010.06.004 · Cited by 251 · see citing works
Cheng, V., Martin, L. J., Elliott, E. M., Kim, J. H., Mount, H. T. J., Taverna, F. A., Roder, J., MacDonald, J. F., Bhambri, A., Collinson, N., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5024-05.2006 · Cited by 246 · see citing works
Towards a comprehensive understanding of anesthetic mechanisms of action: a decade of discovery
Hemmings, H. C., Riegelhaupt, P. M., Kelz, M. B., Solt, K., Eckenhoff, R. G., Orser, B. A., & Goldstein, P. A. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.05.001 · Cited by 244 · see citing works
General Anesthetic Actions on GABAA Receptors
García, P. S., Kolesky, S., & Jenkins, A. (2010) · Current Neuropharmacology · doi:10.2174/157015910790909502 · Cited by 243 · see citing works
Role of endogenous sleep-wake and analgesic systems in anesthesia
Lu, J., Nelson, L. E., Franks, N., Maze, M., Chamberlin, N. L., & Saper, C. B. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21685 · Cited by 230 · see citing works
Self-citationThalamic Microinjection of Nicotine Reverses Sevoflurane-induced Loss of Righting Reflex in the Rat
Alkire, M. T., McReynolds, J. R., Hahn, E. L., & Trivedi, A. N. (2007) · Anesthesiology · doi:10.1097/01.anes.0000270741.33766.24 · Cited by 228 · see citing works
Prostaglandins and adenosine in the regulation of sleep and wakefulness
Huang, Z., Urade, Y., & Hayaishi, O. (2006) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.09.004 · Cited by 224 · see citing works
Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness
White, N. S., & Alkire, M. T. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00103-4 · Cited by 223 · see citing works
General anesthesia and the neural correlates of consciousness
Alkire, M. T., & Miller, J. (2005) · Progress in brain research · doi:10.1016/s0079-6123(05)50017-7 · Cited by 219 · see citing works
Mhuircheartaigh, R. N., Rosenorn-Lanng, D., Wise, R. G., Jbabdi, S., Rogers, R., & Tracey, I. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5516-09.2010 · Cited by 205 · see citing works
Akeju, O., & Brown, E. N. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.04.011 · Cited by 192 · see citing works
Huang, Z., Mochizuki, T., Qu, W., Hong, Z., Watanabe, T., Urade, Y., & Hayaishi, O. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600451103 · Cited by 186 · see citing works
Effects of Dexmedetomidine on Sleep Quality in Critically Ill Patients
Alexopoulou, C., Kondili, Ε., Diamantaki, E., Psarologakis, C., Kokkini, S., Bolaki, M., & Georgopoulos, D. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000361 · Cited by 179 · see citing works
Changes in Resting Neural Connectivity during Propofol Sedation
Stamatakis, E. A., Adapa, R., Absalom, A. R., & Menon, D. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014224 · Cited by 179 · see citing works
Drasbek, K. R., & Jensen, K. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhj055 · Cited by 178 · see citing works
Methylphenidate Actively Induces Emergence from General Anesthesia
Solt, K., Cotten, J. F., Cimenser, A., Wong, K. F. K., Chemali, J. J., & Brown, E. N. (2011) · Anesthesiology · doi:10.1097/aln.0b013e31822e92e5 · Cited by 176 · see citing works
Defining the Propofol Binding Site Location on the GABAA Receptor
Bali, M., & Akabas, M. H. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.1.68 · Cited by 173 · see citing works
Moore, J. T., Chen, J., Han, B., Meng, Q. C., Veasey, S. C., Beck, S. G., & Kelz, M. B. (2012) · Current Biology · doi:10.1016/j.cub.2012.08.042 · Cited by 171 · see citing works
Sleep-wake control and the thalamus
Gent, T. C., Bassetti, C. L., & Adamantidis, A. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.08.002 · Cited by 165 · see citing works
Bennett, C., Voss, L. J., Barnard, J. P. M., & Sleigh, J. W. (2009) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3181a9fc38 · Cited by 164 · see citing works
Hentschke, H., Schwarz, C., & Antkowiak, B. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03843.x · Cited by 163 · see citing works
Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia
Solt, K., Van Dort, C. J., Chemali, J. J., Taylor, N. E., Kenny, J. D., & Brown, E. N. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000117 · Cited by 156 · see citing works
Consciousness Unbound: Toward a Paradigm of General Anesthesia
Mashour, G. A. (2004) · Anesthesiology · doi:10.1097/00000542-200402000-00035 · Cited by 155 · see citing works
Neurobiological effects of gallic acid: current perspectives
Bhuia, M. S., Rahaman, M. M., Islam, T., Bappi, M. H., Sikder, M. I., Hossain, K. N., Akter, F., Prottay, A. A. S., Rokonuzzman, M., Gürer, E. S., et al. (2023) · Chinese Medicine · doi:10.1186/s13020-023-00735-7 · Cited by 154 · see citing works
The Biology of General Anesthesia from Paramecium to Primate
Kelz, M. B., & Mashour, G. A. (2019) · Current Biology · doi:10.1016/j.cub.2019.09.071 · Cited by 151 · see citing works
Coull, J. T., Jones, M. E. P., Egan, T. D., Frith, C., & Maze, M. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2003.12.022 · Cited by 150 · see citing works
Self-citationPatel, S., Wohlfeil, E. R., Rademacher, D. J., Carrier, E. J., Perry, L. J., Kundu, A., Falck, J. R., Nithipatikom, K., Campbell, W. B., & Hillard, C. J. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705334 · Cited by 148 · see citing works
Sleep in the Intensive Care Unit
Pulak, L. M., & Jensen, L. A. (2014) · Journal of Intensive Care Medicine · doi:10.1177/0885066614538749 · Cited by 146 · see citing works
Moulton, E. A., Becerra, L. R., Johnson, A., Burstein, R., & Borsook, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095508 · Cited by 144 · see citing works
Baker, R. H., Gent, T. C., Yang, Q., Parker, S., Vyssotski, A. L., Wisden, W., Brickley, S. G., & Franks, N. P. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1519-14.2014 · Cited by 141 · see citing works
Self-citationTop-down mechanisms of anesthetic-induced unconsciousness
Mashour, G. A. (2014) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2014.00115 · Cited by 134 · see citing works
SLEEPNET: Automated Sleep Staging System via Deep LearningPreprint
Biswal, S., Kulas, J. A., Sun, H., Goparaju, B., Westover, M. B., Bianchi, M. T., & Sun, J. (2017) · arXiv (Cornell University) · doi:10.48550/arxiv.1707.08262 · Cited by 134 · see citing works
Mashour, G. A., & Hudetz, A. G. (2017) · Frontiers in Neural Circuits · doi:10.3389/fncir.2017.00044 · Cited by 133 · see citing works
Lin, J., Anaclet, C., Sergeeva, O. A., & Haas, H. L. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0631-8 · Cited by 130 · see citing works
Kaur, S., Junek, A., Black, M. A., & Semba, K. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1585-07.2008 · Cited by 129 · see citing works
Anesthesia and the neurobiology of consciousness
Mashour, G. A. (2024) · Neuron · doi:10.1016/j.neuron.2024.03.002 · Cited by 127 · see citing works
Zecharia, A. Y., Nelson, L. E., Gent, T. C., Schumacher, M. A., Jurd, R., Rudolph, U., Brickley, S. G., Maze, M., & Franks, N. P. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4997-08.2009 · Cited by 127 · see citing works
Self-citationMajor Role For Tonic GABAA Conductances in Anesthetic Suppression of Intrinsic Neuronal Excitability
Bieda, M. C., & MacIver, M. B. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00223.2004 · Cited by 127 · see citing works
Brain areas that influence general anesthesia
Leung, L. S., Luo, T., Ma, J., & Herrick, I. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.08.001 · Cited by 126 · see citing works
Hong, Z., Huang, Z., Qu, W., Eguchi, N., Urade, Y., & Hayaishi, O. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02991.x · Cited by 124 · see citing works
Hou, R. H., Freeman, C., Langley, R. W., Szabadi, E., & Bradshaw, C. M. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0013-8 · Cited by 123 · see citing works
Cellular and neurochemical basis of sleep stages in the thalamocortical network
Krishnan, G. P., Chauvette, S., Shamie, I., Soltani, S., Timofeev, I., Cash, S. S., Halgren, E., & Bazhenov, M. (2016) · eLife · doi:10.7554/elife.18607 · Cited by 122 · see citing works
Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS)
Frase, L., Piosczyk, H., Zittel, S., Jahn, F., Selhausen, P., Krone, L. B., Feige, B., Mainberger, F., Maier, J. G., Kühn, M., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.65 · Cited by 115 · see citing works
Using EEG to monitor anesthesia drug effects during surgery
Jameson, L. C., & Sloan, T. B. (2006) · Journal of Clinical Monitoring and Computing · doi:10.1007/s10877-006-9044-x · Cited by 115 · see citing works
Alam, M. N., Kumar, S., Bashir, T., Suntsova, N., Methippara, M. M., Szymusiak, R. S., & McGinty, D. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.076927 · Cited by 115 · see citing works
Neurodevelopmental implications of the general anesthesia in neonate and infants
Lee, J. H., Zhang, J., Wei, L., & Yu, S. P. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.03.028 · Cited by 113 · see citing works
Mashour, G. A., Orser, B. A., Avidan, M. S., & Warner, D. S. (2011) · Anesthesiology · doi:10.1097/aln.0b013e31820fc9b6 · Cited by 108 · see citing works
Williams, R. H., Chee, M. J. S., Kroeger, D., Ferrari, L. L., Maratos–Flier, E., Scammell, T. E., & Arrigoni, E. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4838-13.2014 · Cited by 107 · see citing works
Orexin (hypocretin)/dynorphin neurons control GABAergic inputs to tuberomammillary neurons
Eriksson, K. S., Sergeeva, O. A., Selbach, O., & Haas, H. L. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03243.x · Cited by 107 · see citing works
Zecharia, A. Y., Yu, X., Götz, T., Ye, Z., Carr, D. R., Wulff, P., Bettler, B., Vyssotski, A. L., Brickley, S. G., Franks, N. P., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2931-12.2012 · Cited by 106 · see citing works
Self-citationGredell, J. A., Turnquist, P. A., MacIver, M. B., & Pearce, R. A. (2004) · British Journal of Anaesthesia · doi:10.1093/bja/aeh272 · Cited by 106 · see citing works
Alkire, M. T., Asher, C. D., Franciscus, A. M., & Hahn, E. L. (2009) · Anesthesiology · doi:10.1097/aln.0b013e31819c461c · Cited by 105 · see citing works
Electroencephalographic Variation during End Maintenance and Emergence from Surgical Anesthesia
Chander, D., García, P. S., MacColl, J. N., Illing, S., & SLEIGH, J. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106291 · Cited by 105 · see citing works
Anaesthetic mechanisms: update on the challenge of unravelling the mystery of anaesthesia
Lugli, A. K., Yost, C. S., & Kindler, C. H. (2009) · European Journal of Anaesthesiology · doi:10.1097/eja.0b013e32832d6b0f · Cited by 105 · see citing works
State-dependent and reflex drives to the upper airway: basic physiology with clinical implications
Horner, R. L., Hughes, S. W., & Malhotra, A. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00531.2013 · Cited by 104 · see citing works
Qian, Y., Cao, Y., Deng, B., Yang, G., Li, J., Xu, R., Zhang, D., Huang, J., & Rao, Y. (2017) · eLife · doi:10.7554/elife.26519 · Cited by 104 · see citing works
Franks, N. P., & Zecharia, A. Y. (2010) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/s12630-010-9420-3 · Cited by 103 · see citing works
Self-citationWake-related activity of tuberomammillary neurons in rats
Ko, E. M., Estabrooke, I. V., McCarthy, M. T., & Scammell, T. E. (2003) · Brain Research · doi:10.1016/j.brainres.2003.08.044 · Cited by 103 · see citing works
Excitatory pathways from the lateral habenula enable propofol-induced sedation
Gelegen, C., Miracca, G., Ran, M. Z., Harding, E. C., Ye, Z., Yu, X., Tossell, K., Houston, C. M., Yustos, R., Hawkins, E. D., et al. (2018) · Current Biology · doi:10.1016/j.cub.2017.12.050 · Cited by 100 · see citing works
Self-citationGenetic Reporters of Neuronal Activity: c-Fos and G-CaMP6
Hudson, A. E. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2018.01.023 · Cited by 98 · see citing works
Gilsbach, R., & Hein, L. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01533.x · Cited by 97 · see citing works
Vanini, G., Bassana, M., Mast, M., Mondino, A., Cerda, I. H., Phyle, M., Chen, V., Colmenero, A. V., Hambrecht‐Wiedbusch, V. S., & Mashour, G. A. (2020) · Current Biology · doi:10.1016/j.cub.2019.12.063 · Cited by 96 · see citing works
New insights into the molecular mechanisms of general anaesthetics
Chau, P.-L. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00891.x · Cited by 96 · see citing works
Melatonin and anesthesia: a clinical perspective
Naguib, M., Gottumukkala, V. N. R., & Goldstein, P. A. (2006) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00384.x · Cited by 96 · see citing works
Luo, T., & Leung, L.-W. S. (2009) · Anesthesiology · doi:10.1097/aln.0b013e3181b061a0 · Cited by 95 · see citing works
Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex
Raz, A., Grady, S. M., Krause, B. M., Uhlrich, D. J., Manning, K., & Banks, M. I. (2014) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2014.00191 · Cited by 95 · see citing works
Tung, A., & Mendelson, W. B. (2004) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2004.01.003 · Cited by 95 · see citing works
Zheng, X., Huang, H., Liu, J., Li, M., Liu, M., & Luo, T. (2017) · Inflammation · doi:10.1007/s10753-017-0658-6 · Cited by 92 · see citing works
Walsh, J. K., Deacon, S., Dijk, D., & Lundahl, J. (2007) · SLEEP · doi:10.1093/sleep/30.5.593 · Cited by 92 · see citing works
Khisti, R. T., VanDoren, M. J., O’Buckley, T. K., & Morrow, A. L. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02978-0 · Cited by 91 · see citing works
- Authors
- Nelson, L. E., Guo, T. Z., Lu, J., Saper, C. B., Franks, N. P., & Maze, M.
- Affiliations
- Chelsea and Westminster Hospital (GB)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Franks, N. P.
- Venue
- Nature Neuroscience
- Published
- 2002-08-26
- Volume
- 5
- Issue
- 10
- Pages
- 979-984
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2074671627
- Cited by
- 568
- References
- 47
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 20 · 2023: 23 · 2022: 11 · 2021: 18 · 2020: 19 · 2019: 16 · 2018: 21 · 2017: 26 · 2016: 26 · 2015: 17 · 2014: 36 · 2013: 18 · 2012: 27
- FWCI
- 25.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Medical Research Council
- National Institute on Aging (AG09975, P01AG009975)
- National Heart, Lung, and Blood Institute (HL 60292, P50HL060292)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- GABAA receptor, sedation, anesthesia, tuberomammillary nucleus, gabazine, muscimol, propofol, pentobarbital, ketamine, c-fos, sleep regulation, neuronal activation
- MeSH terms
- Anesthesia, Anesthetics, Animals, Hypnotics and Sedatives, Hypothalamic Area, Lateral, Male, Neural Pathways, Rats, Inbred F344, Receptors, GABA-A, Sleep, GABA Agonists, GABA Antagonists, Rats, GABA-A Receptor Agonists, GABA-A Receptor Antagonists
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