A succession of anesthetic endpoints in the Drosophila brain
Abstract
General anesthetics abolish behavioral responsiveness in all animals, and in humans this is accompanied by loss of consciousness. Whether similar target mechanisms and behavioral endpoints exist across species remains controversial, although model organisms have been successfully used to study mechanisms of anesthesia. In Drosophila, a number of key mutants have been characterized as hypersensitive or resistant to general anesthetics by behavioral assays. In order to investigate general anesthesia in the Drosophila brain, local field potential (LFP) recordings were made during incremental exposures to isoflurane in wild‐type and mutant flies. As in higher animals, general anesthesia in flies was found to involve a succession of distinct endpoints. At low doses, isoflurane uncoupled brain activity from ongoing movement, followed by a sudden attenuation in neural correlates of perception. Average LFP activity in the brain was more gradually attenuated with higher doses, followed by loss of movement behavior. Among mutants, a strong correspondence was found between behavioral and LFP sensitivities, thereby suggesting that LFP phenotypes are proximal to the anesthetic's mechanism of action. Finally, genetic and pharmacological analysis revealed that anesthetic sensitivities in the fly brain are, like other arousal states, influenced by dopaminergic activity. These results suggest that volatile anesthetics such as isoflurane may target the same processes that sustain wakefulness and attention in the brain. LFP correlates of general anesthesia in Drosophila provide a powerful new approach to uncovering the nature of these processes. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 1195–1211, 2006
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Drosophila exposed to isoflurane show uncoupling of neural activity from movement at lower doses and cessation of movement at higher doses correlated with local field potential characteristics.
“Drosophila exposed to isoflurane demonstrate an uncoupling of neural activity patterns from movement at lower doses and cessation of movement at higher doses that correlate with local field potential characteristics [155].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [155]
Cites
DeLÉAN, A., Munson, P. J., & Rodbard, D. (1978) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1978.235.2.e97 · Cited by 2,384 · 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
Enzyme changes in neonatal skeletal muscle: effect of thyroid deficiency
Baldwin, K. M., Hooker, A. M., Campbell, P., & Lewis, R. (1978) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1978.235.3.c97 · Cited by 1,118 · see citing works
Rest in Drosophila is a sleep-like state
Hendricks, J. C., Finn, S. M., Panckeri, K. A., Chavkin, J., Williams, J. A., Sehgal, A., & Pack, A. I. (2000) · Neuron · doi:10.1016/s0896-6273(00)80877-6 · Cited by 1,050 · see citing works
Schwaerzel, M., Monastirioti, M., Scholz, H., Friggi-Grelin, F., Birman, S., & Heisenberg, M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-33-10495.2003 · Cited by 871 · see citing works
Associative Odor Learning in Drosophila Abolished by Chemical Ablation of Mushroom Bodies
de Belle, J. S., & Heisenberg, M. (1994) · Science · doi:10.1126/science.8303280 · Cited by 797 · 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
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
The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway
Nelson, L. E., Guo, T. Z., Lu, J., Saper, C. B., Franks, N. P., & Maze, M. (2002) · Nature Neuroscience · doi:10.1038/nn913 · Cited by 568 · see citing works
Friggi‐Grelin, F., Coulom, H., Meller, M., Gomez, D., Hirsh, J., & Birman, S. (2003) · Journal of Neurobiology · doi:10.1002/neu.10185 · Cited by 561 · 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
Molecular mechanisms of general anaesthesia
Franks, N. P., & Lieb, W. R. (1982) · Nature · doi:10.1038/300487a0 · Cited by 436 · see citing works
Increased Synchronization of Neuromagnetic Responses during Conscious Perception
Srinivasan, R., Russell, D. P., Edelman, G. M., & Tononi, G. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-13-05435.1999 · Cited by 428 · see citing works
What Do the Mushroom Bodies Do for the Insect Brain? An IntroductionPreprint
Heisenberg, M. (1998) · Learning & Memory · doi:10.1101/lm.5.1.1 · Cited by 415 · see citing works
Alkire, M. T., Haier, R. J., & Fallon, J. H. (2000) · Consciousness and Cognition · doi:10.1006/ccog.1999.0423 · Cited by 391 · see citing works
Dopaminergic Modulation of Arousal in Drosophila
Waldowski, R. A., van Swinderen, B., & Greenspan, R. J. (2005) · Current Biology · doi:10.1016/j.cub.2005.05.025 · Cited by 359 · see citing works
Odorant-induced oscillations in the mushroom bodies of the locust
Laurent, G., & Naraghi, M. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-05-02993.1994 · Cited by 286 · see citing works
Electrophysiological Correlates of Rest and Activity in Drosophila melanogaster
Nitz, D. A., van Swinderen, B., Tononi, G., & Greenspan, R. J. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01300-3 · Cited by 276 · see citing works
Invariant Reversible QEEG Effects of Anesthetics
John, E. R., Prichep, L. S., Kox, W., Valdés-Sosa, P., Bosch-Bayard, J., Aubert, E., Tom, M., diMichele, F., & Gugino, L. D. (2001) · Consciousness and Cognition · doi:10.1006/ccog.2001.0507 · Cited by 274 · see citing works
John, E. R., & Prichep, L. S. (2005) · Anesthesiology · doi:10.1097/00000542-200502000-00030 · Cited by 250 · 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
SELECTIVE ACTIONS OF VOLATILE GENERAL ANAESTHETICS AT MOLECULAR AND CELLULAR LEVELS
Franks, N. P., & Lieb, W. R. (1993) · British Journal of Anaesthesia · doi:10.1093/bja/71.1.65 · Cited by 218 · see citing works
Multiple Roles for Dopamine inDrosophilaDevelopment
Neckameyer, W. S. (1996) · Developmental Biology · doi:10.1006/dbio.1996.0128 · Cited by 213 · see citing works
Temperature Dependence of the Potency of Volatile General Anesthetics
Franks, N. P., & Lieb, W. R. (1996) · Anesthesiology · doi:10.1097/00000542-199603000-00027 · Cited by 199 · see citing works
Salience modulates 20–30 Hz brain activity in Drosophila
van Swinderen, B., & Greenspan, R. J. (2003) · Nature Neuroscience · doi:10.1038/nn1054 · Cited by 188 · see citing works
Misexpression of the white (w) gene triggers male-male courtship in Drosophila.
Zhang, S. D., & Odenwald, W. F. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5525 · Cited by 164 · 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
In vivo characterization of clinical anaesthesia and its components
Antognini, J. F., & Carstens, E. (2002) · British Journal of Anaesthesia · doi:10.1093/bja/aef156 · Cited by 155 · see citing works
Gail, A. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhg129 · Cited by 151 · see citing works
Naturally Occurring Variability in Anesthetic Potency Among Inbred Mouse Strains
Sonner, J. M., Gong, D., & Eger, E. I. (2000) · Anesthesia & Analgesia · doi:10.1097/00000539-200009000-00042 · Cited by 144 · see citing works
Chang, H.-Y., Grygoruk, A., Brooks, E. S., Ackerson, L. C., Maidment, N. T., Bainton, R. J., & Krantz, D. E. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001742 · Cited by 124 · see citing works
Concepts and correlations relevant to general anaesthesia
Urban, B. W., & Bleckwenn, M. (2002) · British Journal of Anaesthesia · doi:10.1093/bja/aef164 · Cited by 116 · see citing works
Uncoupling of Brain Activity from Movement Defines Arousal States in Drosophila
van Swinderen, B., Nitz, D. A., & Greenspan, R. J. (2004) · Current Biology · doi:10.1016/j.cub.2003.12.057 · Cited by 115 · see citing works
Multiple sites of action of volatile anesthetics in Caenorhabditis elegans.
Morgan, P. G., Sedensky, M. M., & Meneely, P. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.8.2965 · Cited by 110 · see citing works
A neomorphic syntaxin mutation blocks volatile-anesthetic action in <i>Caenorhabditis elegans</i>
van Swinderen, B., Saifee, O., Shebester, L., Roberson, R., Nonet, M. L., & Crowder, C. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2479 · Cited by 106 · see citing works
Self-citationNaturally Occurring Variability in Anesthetic Potency Among Inbred Mouse Strains
Sonner, J. M., Gong, D., & Eger, E. I. (2000) · Anesthesia & Analgesia · doi:10.1213/00000539-200009000-00042 · Cited by 105 · see citing works
Issues in the Design and Interpretation of Minimum Alveolar Anesthetic Concentration (MAC) Studies
Sonner, J. M. (2002) · Anesthesia & Analgesia · doi:10.1213/00000539-200209000-00021 · Cited by 101 · see citing works
Flexibility in a Gene Network Affecting a Simple Behavior in Drosophila melanogaster
van Swinderen, B., & Greenspan, R. J. (2005) · Genetics · doi:10.1534/genetics.104.032631 · Cited by 101 · see citing works
An Unusual Cation Channel Mediates Photic Control of Locomotion in Drosophila
Nash, H. A., Scott, R. L., Lear, B. C., & Allada, R. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01358-1 · Cited by 98 · see citing works
Perchance to dream: Solving the mystery of sleep through genetic analysis
Shaw, P. J., & Franken, P. (2002) · Journal of Neurobiology · doi:10.1002/neu.10167 · Cited by 90 · see citing works
Current assessment of targets and theories of anaesthesia
Urban, B. W. (2002) · British Journal of Anaesthesia · doi:10.1093/bja/aef165 · Cited by 89 · see citing works
The remote roots of consciousness in fruit-fly selective attention?
van Swinderen, B. (2005) · BioEssays · doi:10.1002/bies.20195 · Cited by 87 · see citing works
Campbell, J. L., & Nash, H. A. (2001) · Journal of Neurobiology · doi:10.1002/neu.10009 · Cited by 87 · 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
Use of Drosophila mutants to distinguish among volatile general anesthetics.
Campbell, D. B., & Nash, H. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.6.2135 · Cited by 79 · see citing works
The optomotor responses of some eye mutants ofDrosophila
KALMUS, H. (1943) · Journal of Genetics · doi:10.1007/bf02982936 · Cited by 78 · see citing works
Excitatory and Inhibitory Switches for Courtship in the Brain of Drosophila melanogaster
Broughton, S. J., Kitamoto, T., & Greenspan, R. J. (2004) · Current Biology · doi:10.1016/j.cub.2004.03.037 · Cited by 76 · 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
Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans
Crowder, C. M., Shebester, L., & Schedl, T. (1996) · Anesthesiology · doi:10.1097/00000542-199610000-00027 · Cited by 62 · see citing works
Sandstrom, D. J. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.065748 · Cited by 62 · see citing works
Visually Triggered Neuronal Oscillations in the Pigeon: An Autocorrelation Study of Tectal Activity
Neuenschwander, S., & Varela, F. J. (1993) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1993.tb00939.x · Cited by 56 · see citing works
Koblin, D. D., Deady, J. E., & Eger, E. I. (1982) · Anesthesiology · doi:10.1097/00000542-198201000-00005 · Cited by 47 · see citing works
van Swinderen, B., & Waldowski, R. A. (2003) · Behavioural Processes · doi:10.1016/s0376-6357(03)00131-1 · Cited by 42 · 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
Bekisz, M., & Wróbel, A. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02454.x · Cited by 41 · see citing works
Guan, Z., Scott, R. L., & Nash, H. A. (2000) · Journal of Neurogenetics · doi:10.3109/01677060009083475 · Cited by 35 · see citing works
In vivo genetics of anaesthetic action
Nash, H. A. (2002) · British Journal of Anaesthesia · doi:10.1093/bja/aef159 · Cited by 35 · see citing works
Taniguchi, H., Shishido, E., Takeichi, M., & Nose, A. (2000) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(200001)42:1 · Cited by 35 · see citing works
Influence of general anesthetics on a specific neural pathway in Drosophila melanogaster.
Lin, M., & Nash, H. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.19.10446 · Cited by 33 · see citing works
Goα Regulates Volatile Anesthetic Action in Caenorhabditis elegans
van Swinderen, B., Metz, L. B., Shebester, L., Mendel, J., Sternberg, P. W., & Crowder, C. M. (2001) · Genetics · doi:10.1093/genetics/158.2.643 · Cited by 32 · see citing works
What can in vivo electrophysiology in animal models tell us about mechanisms of anaesthesia?
Vahle-Hinz, C., & Detsch, O. (2002) · British Journal of Anaesthesia · doi:10.1093/bja/aef166 · Cited by 32 · see citing works
Bernards, C. M., Kern, C. G., & Cullen, B. F. (1996) · Anesthesiology · doi:10.1097/00000542-199607000-00013 · Cited by 29 · see citing works
Nishikawa, K.-I., & Kidokoro, Y. (1999) · Anesthesiology · doi:10.1097/00000542-199906000-00026 · Cited by 29 · see citing works
Calreticulin Mediates Anesthetic Sensitivity in Drosophila melanogaster
Gamo, S., Tomida, J., Dodo, K., et al. (2003) · Anesthesiology · doi:10.1097/00000542-200310000-00019 · Cited by 23 · see citing works
The Visually-Induced Jump Response of Drosophila Melanogaster is Sensitive to Volatile Anesthetics
Campbell, J. L., & Nash, H. A. (1998) · Journal of Neurogenetics · doi:10.3109/01677069809108561 · Cited by 20 · see citing works
Walcourt, A., Scott, R. L., & Nash, H. A. (2001) · Anesthesia & Analgesia · doi:10.1213/00000539-200102000-00047 · Cited by 20 · see citing works
Walcourt, A., & Ide, D. (1998) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(98)00105-8 · Cited by 15 · see citing works
The neuronal basis of the anesthetic state: A comparative physiological approach
Kirschfeld, K., & Baier-Rogowski, V. (1988) · Biological Cybernetics · doi:10.1007/bf00363951 · Cited by 12 · see citing works
Rajaram, S., & Nash, H. A. (2004) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000113548.27457.a3 · Cited by 11 · see citing works
Nash, H. A. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80055-4 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
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
The sodium leak channel, NALCN, in health and disease
Cochet-Bissuel, M., Lory, P., & Monteil, A. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00132 · Cited by 172 · 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
Mashour, G. A. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.09.009 · Cited by 92 · 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
Cohen, D., van Swinderen, B., & Tsuchiya, N. (2018) · eneuro · doi:10.1523/eneuro.0329-17.2018 · Cited by 23 · see citing works
- Authors
- van Swinderen, B.
- Venue
- Journal of Neurobiology
- Publisher
- Wiley
- Published
- 2006-07-20
- Volume
- 66
- Issue
- 11
- Pages
- 1195-1211
- ISSN
- 0022-3034 (ISSN-L)
- 1097-4695
- OpenAlex
- W2027025589
- Cited by
- 33
- References
- 70
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 4 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 4
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- general anesthesia, isoflurane, Drosophila brain, local field potentials, anesthetic sensitivity, dopaminergic activity, wakefulness, attention, loss of consciousness, neural correlates of perception, movement behavior
- MeSH terms
- Animals, Brain, Dose-Response Relationship, Drug, Drosophila, Electrophysiology, Evoked Potentials, Isoflurane, Phenotype, Sleep, Anesthetics, General, Animals, Genetically Modified
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