Genetic and anatomical basis of the barrier separating wakefulness and anesthetic-induced unresponsiveness
Open accessAbstract
A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Loss-of-function sleepless mutants show resistance to induction of and emergence from anesthesia similar to shaker mutant flies.
“Anesthetic responses in loss-of-function sleepless mutants exhibit similar resistance to induction of and emergence from anesthesia, phenocopying responses of shaker mutant flies [58].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [58]
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 [58]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Two-Process Model of Sleep Regulation
Binder, M. D., Hirokawa, N., & Windhorst, U. (2008) · Springer eBooks · doi:10.1007/978-3-540-29678-2_6166 · Cited by 3,895 · see citing works
The sleep switch: hypothalamic control of sleep and wakefulness
Saper, C. B., Chou, T. C., & Scammell, T. E. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)02002-6 · Cited by 1,656 · see citing works
Correlates of Sleep and Waking in Drosophila melanogaster
Shaw, P. J., Cirelli, C., Greenspan, R. J., & Tononi, G. (2000) · Science · doi:10.1126/science.287.5459.1834 · Cited by 1,300 · see citing works
Sleep and arousal: thalamocortical mechanisms
McCormick, D. A., & Bal, T. (1997) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.20.1.185 · Cited by 1,267 · 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
A putative flip–flop switch for control of REM sleep
Lu, J., Sherman, D. L., Devor, M. G., & Saper, C. B. (2006) · Nature · doi:10.1038/nature04767 · Cited by 1,219 · see citing works
Multilineage Transcriptional Priming and Determination of Alternate Hematopoietic Cell Fates
Laslo, P., Spooner, C. J., Warmflash, A., Lancki, D. W., Lee, H.-J., Sciammas, R., Gantner, B. N., Dinner, A. R., & Singh, H. (2006) · Cell · doi:10.1016/j.cell.2006.06.052 · Cited by 632 · see citing works
Dopamine Is a Regulator of Arousal in the Fruit Fly
Kume, K., Kume, S., Park, S. K., Hirsh, J., & Jackson, F. R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2048-05.2005 · Cited by 597 · 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
TREK-1, a K+ channel involved in neuroprotection and general anesthesia
Heurteaux, C., Guy, N., Laigle, C., Blondeau, N., Duprat, F., Mazzuca, M., Lang‐Lazdunski, L., Widmann, C., Zanzouri, M., Romey, G., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600234 · Cited by 534 · see citing works
Stress response genes protect against lethal effects of sleep deprivation in Drosophila
Shaw, P. J., Tononi, G., Greenspan, R. J., & Robinson, D. F. (2002) · Nature · doi:10.1038/417287a · Cited by 479 · see citing works
Reduced sleep in Drosophila Shaker mutants
Cirelli, C., Bushey, D., Hill, S., Huber, R., Kreber, R. A., Ganetzky, B., & Tononi, G. (2005) · Nature · doi:10.1038/nature03486 · Cited by 474 · see citing works
Sleep in Drosophila is regulated by adult mushroom bodies
Joiner, W. J., Crocker, A. J., White, B. H., & Sehgal, A. (2006) · Nature · doi:10.1038/nature04811 · Cited by 455 · see citing works
Self-citationSleep Homeostasis in Drosophila Melanogaster
Huber, R., Hill, S., Holladay, C., Biesiadecki, M., Tononi, G., & Cirelli, C. (2004) · SLEEP · doi:10.1093/sleep/27.4.628 · Cited by 412 · see citing works
Lu, B., Su, Y., Das, S., Liu, J., Xia, J., & Ren, D. (2007) · Cell · doi:10.1016/j.cell.2007.02.041 · Cited by 381 · see citing works
Identification of SLEEPLESS, a sleep-promoting factor
Koh, K., Joiner, W. J., Wu, M. N., Yue, Z., Smith, C. J., & Sehgal, A. (2008) · Science · doi:10.1126/science.1155942 · Cited by 347 · see citing works
Self-citationPositive feedback in cellular control systems
Mitrophanov, A. Y., & Groisman, E. A. (2008) · BioEssays · doi:10.1002/bies.20769 · Cited by 272 · see citing works
Sleep, Anesthesiology, and the Neurobiology of Arousal State Control
Lydic, R., & Baghdoyan, H. A. (2005) · Anesthesiology · doi:10.1097/00000542-200512000-00024 · Cited by 251 · 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
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
Friedman, E. B., Sun, Y., Moore, J. T., Hung, H.-T., Meng, Q. C., Perera, P., Joiner, W. J., Thomas, S. A., Eckenhoff, R. G., Sehgal, A., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011903 · Cited by 218 · see citing works
Self-citationHendricks, J. C., Lu, S., Kume, K., Yin, J. C. P., Yang, Z., & Sehgal, A. (2003) · Journal of Biological Rhythms · doi:10.1177/0748730402239673 · Cited by 183 · see citing works
Self-citationModelling general anaesthesia as a first-order phase transition in the cortex
Steyn‐Ross, M. L., Steyn‐Ross, D. A., & Sleigh, J. W. (2004) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2004.02.001 · Cited by 137 · see citing works
Humphrey, J. A., Hamming, K. S. C., Thacker, C. M., Scott, R. L., Sedensky, M. M., Snutch, T. P., Morgan, P. G., & Nash, H. A. (2007) · Current Biology · doi:10.1016/j.cub.2007.02.037 · Cited by 118 · see citing works
Wu, M. N., Joiner, W. J., Dean, T., Yue, Z., Smith, C. J., Chen, D., Hoshi, T., Sehgal, A., & Koh, K. (2009) · Nature Neuroscience · doi:10.1038/nn.2454 · Cited by 113 · see citing works
Self-citationTung, A., Szafran, M. J., Bluhm, B., & Mendelson, W. B. (2002) · Anesthesiology · doi:10.1097/00000542-200210000-00024 · Cited by 112 · 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
Membrane Bistability in Thalamic Reticular Neurons During Spindle Oscillations
Fuentealba, P., Timofeev, I., Bazhenov, M., B, T. J. S. A., & Steriade, M. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00552.2004 · Cited by 97 · see citing works
Krishnan, K. S., & Nash, H. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8632 · Cited by 87 · see citing works
Steyn‐Ross, M. L., Steyn‐Ross, D. A., Sleigh, J. W., & Wilcocks, L. C. (2001) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.64.011917 · Cited by 83 · see citing works
Effect of Anesthetics and a Convulsant on Normal and Mutant Caenorhabditis elegans
Morgan, P. G., & CASCORBI, H. F. (1985) · Anesthesiology · doi:10.1097/00000542-198506000-00007 · Cited by 77 · see citing works
Pal, D., Lipinski, W. J., Walker, A. J., Turner, A. M., & Mashour, G. A. (2011) · Anesthesiology · doi:10.1097/aln.0b013e318204e064 · Cited by 71 · see citing works
A sleep/wake circuit controls isoflurane sensitivity in Drosophila
Kottler, B., Bao, H., Zalucki, O., Imlach, W., Troup, M., van Alphen, B., Paulk, A., Zhang, B., & van Swinderen, B. (2013) · Current Biology · doi:10.1016/j.cub.2013.02.021 · Cited by 63 · see citing works
Drosophila melanogaster as a Model for Study of General Anesthesia
Allada, R., & Nash, H. A. (1993) · Anesthesia & Analgesia · doi:10.1213/00000539-199307000-00005 · Cited by 62 · see citing works
Isoflurane Anesthesia Does Not Satisfy the Homeostatic Need for Rapid Eye Movement Sleep
Mashour, G. A., Lipinski, W. J., Matlen, L. B., Walker, A. J., Turner, A. M., Schoen, W., Lee, U., & Poe, G. R. (2010) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3181d3e861 · Cited by 58 · see citing works
Tweaking biological switches through a better understanding of bistability behavior
Chatterjee, A., Kaznessis, Y. N., & Hu, W. (2008) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2008.08.010 · Cited by 48 · see citing works
Hysteresis vs. Graded Responses: The Connections Make All the Difference
Ninfa, A. J., & Mayo, A. (2004) · Science s STKE · doi:10.1126/stke.2322004pe20 · Cited by 46 · see citing works
Leibovitch, B. A., Campbell, D. B., Krishnan, K. S., & Nash, H. A. (1995) · Journal of Neurogenetics · doi:10.3109/01677069509083455 · Cited by 42 · see citing works
Quantitative Autoradiography of Halothane Binding in Rat Brain
Eckenhoff, M. F., & Eckenhoff, R. G. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37402-6 · Cited by 39 · see citing works
Halothane-induced Hypnosis Is Not Accompanied by Inactivation of Orexinergic Output in Rodents
Gompf, H. S., Chen, J., Sun, Y., Yanagisawa, M., Aston‐Jones, G., & Kelz, M. B. (2009) · Anesthesiology · doi:10.1097/aln.0b013e3181b764b3 · Cited by 37 · see citing works
Self-citationAnesthesia's Second Power: Probing the Mind
Beecher, H. K. (1947) · Science · doi:10.1126/science.105.2720.164 · Cited by 29 · see citing works
Increased volatile anesthetic requirement in short-sleeping Drosophila mutants
Weber, B., Schaper, C., Bushey, D., Rohlfs, M., Steinfath, M., Tononi, G., Cirelli, C., Scholz, J., & Bein, B. (2009) · Anesthesiology · doi:10.1097/aln.0b013e3181942df2 · Cited by 26 · see citing works
Optical Reversal of Halothane-Induced Immobility in C. elegans
Singaram, V. K., Somerlot, B. H., Falk, S. A., Falk, M. J., Sedensky, M. M., & Morgan, P. G. (2011) · Current Biology · doi:10.1016/j.cub.2011.10.042 · Cited by 22 · see citing works
Investigating paradoxical hysteresis effects in the mouse neocortical slice model
Voss, L. J., Brock, M., Carlsson, C., Steyn‐Ross, D. A., Steyn‐Ross, M. L., & Sleigh, J. W. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.11.045 · Cited by 14 · see citing works
Flagged first, then by citations
1 of the 45 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Explosive transitions in complex networks’ structure and dynamics: Percolation and synchronization
Boccaletti, S., Almendral, J. A., Guan, S., Leyva, I., Liu, Z., Sendiña–Nadal, I., Wang, Z., & Zou, Y. (2016) · Physics Reports · doi:10.1016/j.physrep.2016.10.004 · Cited by 377 · see citing works
Forward-genetics analysis of sleep in randomly mutagenized mice
Funato, H., Miyoshi, C., Fujiyama, T., Kanda, T., Sato, M., Wang, Z., Ma, J., Nakane, S., Tomita, J., Ikkyu, A., et al. (2016) · Nature · doi:10.1038/nature20142 · Cited by 327 · see citing works
Unraveling the evolutionary determinants of sleep
Joiner, W. J. (2016) · Current Biology · doi:10.1016/j.cub.2016.08.068 · Cited by 232 · see citing works
Self-citationA Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability
Flourakis, M., Kula-Eversole, E., Hutchison, A. L., Han, T. H., Aranda, K., Moose, D. L., White, K. P., Dinner, A. R., Lear, B. C., Ren, D., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.036 · Cited by 217 · see citing works
Explosive phenomena in complex networks
D’Souza, R. M., Gómez‐Gardeñes, J., Nagler, J., & Arenas, A. (2019) · Advances In Physics · doi:10.1080/00018732.2019.1650450 · Cited by 201 · see citing works
Perioperative Neurocognitive Disorder
Eckenhoff, R. G., Maze, M., Xie, Z., Culley, D. J., Goodlin, S. J., Zuo, Z., Wei, H., Whittington, R. A., Terrando, N., Orser, B. A., et al. (2019) · Anesthesiology · doi:10.1097/aln.0000000000002956 · Cited by 180 · see citing works
Kim, M., Mashour, G. A., Moraes, S.-B., Vanini, G., Tarnal, V., Janke, E., Hudetz, A. G., & Lee, U. (2016) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2016.00001 · Cited by 162 · 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
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
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
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
Differential regulation of the Drosophila sleep homeostat by circadian and arousal inputs
Ni, J. D., Gurav, A. S., Liu, W., Ogunmowo, T. H., Hackbart, H., Elsheikh, A., Verdegaal, A. A., & Montell, C. (2019) · eLife · doi:10.7554/elife.40487 · Cited by 93 · see citing works
Using Drosophila as an integrated model to study mild repetitive traumatic brain injury
Barekat, A., Gonzalez, A., Mauntz, R. E., Kotzebue, R. W., Molina, B., El-Mecharrafie, N., Conner, C. J., Garza, S., Melkani, G. C., Joiner, W. J., et al. (2016) · Scientific Reports · doi:10.1038/srep25252 · Cited by 87 · see citing works
Self-citationEscape From Oblivion: Neural Mechanisms of Emergence From General Anesthesia
Kelz, M. B., García, P. S., Mashour, G. A., & Solt, K. (2019) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000004006 · Cited by 74 · see citing works
Self-citationKim, H., Moon, J.-Y., Mashour, G. A., & Lee, U. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006424 · Cited by 67 · see citing works
Jang, H., Mashour, G. A., Hudetz, A. G., & Huang, Z. (2024) · Nature Communications · doi:10.1038/s41467-024-53299-x · Cited by 54 · see citing works
Wu, T., Zhang, X., & Liu, Z. (2022) · Frontiers of Physics · doi:10.1007/s11467-022-1161-6 · Cited by 53 · see citing works
The Neurobiology of Anesthetic Emergence
Tarnal, V., Vlisides, P. E., & Mashour, G. A. (2015) · Journal of Neurosurgical Anesthesiology · doi:10.1097/ana.0000000000000212 · Cited by 47 · see citing works
New insights into the physiology and pathophysiology of the atypical sodium leak channel NALCN
Monteil, A., Guérineau, N. C., Gil‐Nagel, A., Parra‐Díaz, P., Lory, P., & Senatore, A. (2023) · Physiological Reviews · doi:10.1152/physrev.00014.2022 · Cited by 48 · see citing works
The Neurobiological Basis of Sleep and Sleep Disorders
Joiner, W. J. (2018) · Physiology · doi:10.1152/physiol.00013.2018 · Cited by 51 · see citing works
Self-citationA stochastic basis for neural inertia in emergence from general anaesthesia
Proekt, A., & Hudson, A. E. (2018) · British Journal of Anaesthesia · doi:10.1016/j.bja.2018.02.035 · Cited by 43 · see citing works
Asymmetric neural dynamics characterize loss and recovery of consciousness
Huang, Z., Tarnal, V., Vlisides, P. E., Janke, E., McKinney, A., Picton, P., Mashour, G. A., & Hudetz, A. G. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118042 · Cited by 42 · see citing works
Re-examining the role of the dorsal fan-shaped body in promoting sleep in Drosophila
De, J., Wu, M., Lambatan, V., Hua, Y., & Joiner, W. J. (2023) · Current Biology · doi:10.1016/j.cub.2023.07.043 · Cited by 42 · see citing works
Self-citationSevoflurane Induces Coherent Slow-Delta Oscillations in Rats
Guidera, J. A., Taylor, N. E., Lee, J. T., Vlasov, K. Y., Pei, J., Stephen, E. P., Mayo, J. P., Brown, E. N., & Solt, K. (2017) · Frontiers in Neural Circuits · doi:10.3389/fncir.2017.00036 · Cited by 41 · see citing works
Brainstem node for loss of consciousness due to GABAA receptor-active anesthetics
Minert, A., & Devor, M. G. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.10.001 · Cited by 41 · see citing works
Aging and Autophagic Function Influences the Progressive Decline of Adult Drosophila Behaviors
Ratliff, E. P., Mauntz, R. E., Kotzebue, R. W., Gonzalez, A., Achal, M., Barekat, A., Finley, K. A., Sparhawk, J. M., Robinson, J. E., Herr, D. R., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132768 · Cited by 40 · see citing works
Self-citationMcKinstry-Wu, A. R., Wasilczuk, A. Z., Harrison, B. A., Bedell, V. M., Sridharan, M. J., Breig, J. J., Pack, M. A., Kelz, M. B., & Proekt, A. (2019) · eLife · doi:10.7554/elife.50143 · Cited by 39 · see citing works
Self-citationMitochondrial Function in Astrocytes Is Essential for Normal Emergence from Anesthesia in Mice
Ramadasan-Nair, R., Hui, J., Itsara, L. S., Morgan, P. G., & Sedensky, M. M. (2019) · Anesthesiology · doi:10.1097/aln.0000000000002528 · Cited by 36 · see citing works
Challenges and Demand for Modeling Disorders of Consciousness following Traumatic Brain Injury
O'Donnell, J. C., Browne, K., Kilbaugh, T. J., Chen, H., Whyte, J., & Cullen, D. (2018) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.12.015 · Cited by 15 · see citing works
Sepúlveda, P., Tapia, L. F., & Monsalves, S. (2019) · Anaesthesia · doi:10.1111/anae.14609 · Cited by 29 · see citing works
Protocol for the Reconstructing Consciousness and Cognition (ReCCognition) Study
Maier, K. L., McKinstry-Wu, A. R., Palanca, B. J. A., Tarnal, V., Blain‐Moraes, S., Basner, M., Avidan, M. S., Mashour, G. A., & Kelz, M. B. (2017) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00284 · Cited by 30 · see citing works
Self-citationSlow Waves Form Expanding, Memory-Rich Mesostates Steered by Local Excitability in Fading Anesthesia
Pazienti, A., Galluzzi, A., Dasilva, M., Sanchez-Vives, M. V., & Mattia, M. (2021) · iScience · doi:10.1016/j.isci.2022.103918 · Cited by 28 · see citing works
Han, B., McCarren, H. S., O’Neill, D., & Kelz, M. B. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000383 · Cited by 28 · see citing works
Self-citationEvidence of hysteresis in propofol pharmacodynamics
Sepúlveda, P., Carrasco, E., Tapia, L. F., Ramos, M., Cruz, F., Conget, P. A., Olivares, B., & Cortínez, I. (2017) · Anaesthesia · doi:10.1111/anae.14009 · Cited by 29 · see citing works
Hashemi, M., Hutt, A., Hight, D., & SLEIGH, J. W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0179286 · Cited by 25 · see citing works
Explaining anaesthetic hysteresis with effect-site equilibration
Proekt, A., & Kelz, M. B. (2020) · British Journal of Anaesthesia · doi:10.1016/j.bja.2020.09.022 · Cited by 22 · see citing works
Self-citationEmergence of explosive synchronization bombs in networks of oscillators
Arola-Fernández, L., Faci-Lázaro, S., Skardal, P. S., Boghiu, E.-C., Gómez‐Gardeñes, J., & Arenas, À. (2022) · Communications Physics · doi:10.1038/s42005-022-01039-2 · Cited by 19 · see citing works
Schrödinger's cat: anaesthetised and not!
Proekt, A., & Kelz, M. B. (2017) · British Journal of Anaesthesia · doi:10.1016/j.bja.2017.11.068 · Cited by 19 · see citing works
Self-citationWasilczuk, A. Z., Harrison, B. A., Kwasniewska, P., Ku, B., Kelz, M. B., McKinstry-Wu, A. R., & Proekt, A. (2020) · British Journal of Anaesthesia · doi:10.1016/j.bja.2020.05.031 · Cited by 19 · see citing works
Self-citationReduced Nav1.6 sodium channel activity in mice increases in vivo sensitivity to volatile anesthetics
Pal, D., Jones, J. M., Wisidagamage, S., Meisler, M. H., & Mashour, G. A. (2015) · PLOS ONE · doi:10.1371/journal.pone.0134960 · Cited by 17 · see citing works
Homeostatic dynamics, hysteresis and synchronization in a low-dimensional model of burst suppression
Liu, S., & Ching, S. (2016) · Journal of Mathematical Biology · doi:10.1007/s00285-016-1048-7 · Cited by 15 · see citing works
Development and validation of brain target controlled infusion of propofol in mice
Shortal, B. P., Reitz, S. L., Aggarwal, A., Meng, Q. C., McKinstry-Wu, A. R., Kelz, M. B., & Proekt, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194949 · Cited by 15 · see citing works
Self-citationThe Inert Brain: Explaining Neural Inertia as Post-anaesthetic Sleep Inertia
Luppi, A. I., Spindler, L. R. B., Menon, D. K., & Stamatakis, E. A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.643871 · Cited by 14 · see citing works
The pharmacology of human sleep, a work in progress?
Idzikowski, C. (2014) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2014.01.002 · Cited by 12 · see citing works
Ferreira, A., Correia, R., Vide, S., Ferreira, A. D., Kelz, M. B., Mendes, J. G., Nunes, C. S., & Amorim, P. (2018) · Journal of Neurosurgical Anesthesiology · doi:10.1097/ana.0000000000000559 · Cited by 11 · see citing works
Self-citationMurakami, K., Palermo, J., Stanhope, B. A., Gibbs, A. G., & Keene, A. C. (2021) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkab199 · Cited by 11 · see citing works
Kim, M., Harris, R. E., DaSilva, A. F. M., & Lee, U. (2022) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2022.815099 · Cited by 10 · see citing works
Modulation and neural correlates of postmating sleep plasticity in Drosophila females
Duhart, J. M., Buchler, J. R., Inami, S., Kennedy, K. J., Jenny, B. P., Afonso, D. J. S., & Koh, K. (2023) · Current Biology · doi:10.1016/j.cub.2023.05.054 · Cited by 10 · see citing works
Self-citationNeural Inertia: A Sticky Situation for Anesthesia
McKinstry-Wu, A. R., Proekt, A., & Kelz, M. B. (2020) · Journal of Neurosurgical Anesthesiology · doi:10.1097/ana.0000000000000687 · Cited by 10 · see citing works
Self-citationUsing Drosophila to Understand General Anesthesia: From Synapses to Behavior
Karunanithi, S., Troup, M., & van Swinderen, B. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2018.02.003 · Cited by 8 · see citing works
Isolated forearm technique and consciousness
Russell, F., & Wang, M. (2013) · Anaesthesia · doi:10.1111/anae.12547 · Cited by 9 · see citing works
A probabilistic model of behavioural emergence from general anaesthesia in mice
Stone, M. E., Kelz, M. B., Proekt, A., & Wasilczuk, A. Z. (2025) · British Journal of Anaesthesia · doi:10.1016/j.bja.2025.02.036 · Cited by 7 · see citing works
Self-citationGhosh, R., Anwar, M. S., Shrimali, M. D., & Ghosh, D. (2025) · Chaos An Interdisciplinary Journal of Nonlinear Science · doi:10.1063/5.0289362 · Cited by 6 · see citing works
Distinct Neural Mechanisms Between Anesthesia Induction and Emergence: A Narrative Review
Zhang, D., & Wei, Y. (2024) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000007114 · Cited by 6 · see citing works
Guillaumin, M. C. C., Harding, C. D., Krone, L. B., Yamagata, T., Kahn, M. C., Blanco‐Duque, C., Banks, G. T., Achermann, P., Behn, C. D., Nolan, P. M., et al. (2025) · Current Biology · doi:10.1016/j.cub.2025.02.053 · Cited by 6 · see citing works
Adapa, R. (2017) · Springer eBooks · doi:10.1007/978-3-319-47609-4_4 · Cited by 6 · see citing works
Electroencephalographic Evidence for Individual Neural Inertia in Mice That Decreases With Time
Wasilczuk, A. Z., Meng, Q. C., & McKinstry-Wu, A. R. (2022) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2021.787612 · Cited by 5 · see citing works
Topologically induced suppression of explosive synchronization
Miranda, M., Frasca, M., & Estrada, E. (2023) · Chaos An Interdisciplinary Journal of Nonlinear Science · doi:10.1063/5.0142418 · Cited by 4 · see citing works
Xenon Anesthesia and CT: Noninvasive Measures of Brain Anesthetic Concentration
McKinstry-Wu, A. R., Carspecken, C. W., Proekt, A., & Kelz, M. B. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2018.01.011 · Cited by 4 · see citing works
Self-citationSleep and Anesthesia: Different States with Shared Pathophysiological Traits
Hillman, D. R., Kaw, R. K., & Lydic, R. (2017) · Springer eBooks · doi:10.1007/978-1-4939-6578-6_10 · Cited by 3 · see citing works
Dementia and sensitivity to anesthetics
Mashour, G. A., & Avidan, M. S. (2014) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/s12630-014-0166-1 · Cited by 3 · see citing works
Coetzee, J. F., Links, A., & Levin, A. I. (2021) · Southern African Journal of Anaesthesia and Analgesia · doi:10.36303/sajaa.2021.27.2.2583 · Cited by 2 · see citing works
Olšovský, J., & Beránek, M. (2007) · PubMed · Cited by 2 · see citing works
Stochastic nature of neural inertia
Lee, U., & Mashour, G. A. (2018) · British Journal of Anaesthesia · doi:10.1016/j.bja.2018.04.018 · Cited by 2 · see citing works
Guillaumin, M. C. C., Harding, C. D., Krone, L. B., Yamagata, T., Kahn, M. C., Blanco‐Duque, C., Banks, G. T., Nolan, P. M., Peirson, S. N., & Vyazovskiy, V. V. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.11.540034 · Cited by 2 · see citing works
Daplan, E., Turin, L., & Skoulakis, E. M. C. (2025) · Anesthesia Research · doi:10.3390/anesthres2020012 · Cited by 1 · see citing works
Proekt, A. (2019) · Cambridge University Press eBooks · doi:10.1017/9781316402504.002 · Cited by 2 · see citing works
The 2020 Pittendrigh/Aschoff Lecture: My Circadian Journey
Sehgal, A. (2021) · Journal of Biological Rhythms · doi:10.1177/0748730420982398 · Cited by 1 · see citing works
Self-citationUnconventional monitoring methods: can BIS® predict airway obstruction?
Marco, P. D., & Iannuccelli, F. (2018) · Minerva Anestesiologica · doi:10.23736/s0375-9393.18.12762-3 · Cited by 1 · see citing works
Take Off, Landing, and Fly Anesthesia
Sanders, R. D., & Maze, M. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003788
Future of Critical Care Medicine
Kofke, W. A., & Kositratna, G. (2016) · Springer eBooks · doi:10.1007/978-3-319-30454-0_15
Coordinated activity of sleep and arousal neurons for stabilizing sleep/wake states in DrosophilaPreprint
Ni, J. D., Ogunmowo, T. H., Hackbart, H., Elsheikh, A., Gurav, A. S., Verdegaal, A. A., & Montell, C. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/243444
Zhang, Y., Wang, Y., Wang, C., Yan, F., Wang, Q., & Huang, L. (2018) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2018.07.008
Blackwood, E. B., Shortal, B. P., & Proekt, A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.07.467591
MacIver, M. B. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734986474.793555990
Mulkey, D. K., & Cleary, C. M. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734986474.793573875
Future Advances in Neuroanesthesia
Kofke, W. A., & Hensley, J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-93273-8.00030-4
Molina, B., Rojas, J. J., El-Mecharrafie, N., Ratliff, E. P., Lipinski, M. M., & Finley, K. D. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.10.637558
Reanimation of rodents: an animal model for cognitive recovery from anaesthesia
McKinstry-Wu, A. R., & Kelz, M. B. (2025) · British Journal of Anaesthesia · doi:10.1016/j.bja.2025.05.022
Self-citationModulatory mechanism of the paraventricular thalamus (PVT) under general anesthesia
Li, J., Wei, Y., & Zhang, D. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1732125
Bouasse, M. (2017) · doi:10.70675/6ade06edz19aez4babzb28bzc209b78e30e4
- Authors
- Joiner, W. J., Friedman, E. B., Hung, H.-T., Koh, K., Sowcik, M., Sehgal, A., & Kelz, M. B.
- Affiliations
- University of California San Diego (US)
- Howard Hughes Medical Institute (US)
- Thomas Jefferson University (US)
- University of Pennsylvania (US)
- Corresponding author
- Kelz, Max B.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-09-05
- Volume
- 9
- Issue
- 9
- Pages
- e1003605
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3764144
- OpenAlex
- W2096100413
- Cited by
- 82
- References
- 45
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 10 · 2018: 13 · 2017: 8 · 2016: 7 · 2015: 5 · 2014: 5 · 2013: 2
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- The Medicine Forum (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- Whitehall Foundation
- University of Pennsylvania
- Institute for Translational Medicine and Therapeutics
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM088156, R01GM088221)
- National Institute of Neurological Disorders and Stroke (R01NS072431)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- wakefulness, sleep homeostasis, arousal regulation, bistable switch, SH gene, sodium channels, loss-of-function mutations, homeostatic sleep drive, coma, persistent vegetative state, sleep-wake cycle
- MeSH terms
- Animals, Arousal, Brain, Circadian Rhythm, Drosophila melanogaster, Homeostasis, Humans, Ion Channels, Membrane Proteins, Mutation, Neurons, Sleep, Wakefulness, Drosophila Proteins, Shaker Superfamily of Potassium Channels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
