Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia
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Significance: Although dopamine is known to promote wakefulness, the specific dopamine circuits in the brain that regulate arousal are not clear. Here we report that selective optogenetic stimulation of ventral tegmental area (VTA) dopamine neurons in mice produces a powerful arousal response sufficient to restore conscious behaviors, including the righting reflex, during continuous, steady-state general anesthesia. Although previous studies found that VTA dopamine neurons do not appear to play a central role in regulating sleep–wake transitions, our findings demonstrate that selective stimulation of these neurons is sufficient to induce the transition from an unconscious, anesthetized state to an awake state. These results suggest that VTA DA neurons play a critical role in promoting wakefulness.
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Causal reactivation of some wake-promoting neurons during emergence has been explored with electrical, optogenetic, and chemogenetic methods in rodents and suggested in humans.
“the causal reactivation of some wake-promoting neurons during emergence from the anesthetic state has been explored using approaches such as electrical stimulation, optogenetics, and chemogenetics [115–118] in rodents and suggested in humans [119].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [115]
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
Millisecond-timescale, genetically targeted optical control of neural activity
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., & Deisseroth, K. A. (2005) · Nature Neuroscience · doi:10.1038/nn1525 · Cited by 4,831 · see citing works
Self-citationOlds, J., & Milner, P. (1954) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0058775 · Cited by 3,176 · see citing works
Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry
Kravitz, A. V., Freeze, B. S., Parker, P. R. L., Kay, K., Thwin, M. T., Deisseroth, K., & Kreitzer, A. C. (2010) · Nature · doi:10.1038/nature09159 · Cited by 1,885 · see citing works
General 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
Self-citationNeuron-type-specific signals for reward and punishment in the ventral tegmental area
Cohen, J. Y., Haesler, S., Vong, L., Lowell, B. B., & Uchida, N. (2012) · Nature · doi:10.1038/nature10754 · Cited by 1,318 · 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
Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning
Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G. D., Bonci, A., de Lecea, L., & Deisseroth, K. (2009) · Science · doi:10.1126/science.1168878 · Cited by 1,266 · see citing works
Miller, R. D. (2005) · Cited by 1,240 · see citing works
A causal link between prediction errors, dopamine neurons and learning
Steinberg, E. E., Keiflin, R., Boivin, J. R., Witten, I. B., Deisseroth, K. A., & Janak, P. H. (2013) · Nature Neuroscience · doi:10.1038/nn.3413 · Cited by 879 · 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
Self-citationElectroencephalogram signatures of loss and recovery of consciousness from propofol
Purdon, P. L., Pierce, E. T., Mukamel, E. A., Prerau, M. J., Walsh, J. L., Wong, K. F. K., Salazar-Gomez, A. F., Harrell, P. G., Sampson, A. L., Cimenser, A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221180110 · Cited by 854 · see citing works
Self-citationAmphetamine, past and present – a pharmacological and clinical perspective
Heal, D. J., Smith, S. L., Gosden, J., & Nutt, D. (2013) · Journal of Psychopharmacology · doi:10.1177/0269881113482532 · Cited by 622 · see citing works
Ventral Tegmental Area Neurons in Learned Appetitive Behavior and Positive Reinforcement
Fields, H. L., Hjelmstad, G. O., Margolis, E. B., & Nicola, S. M. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094341 · Cited by 611 · 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
Self-citationEmerging 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
Kennedy, D., & Norman, C. A. (2005) · Science · doi:10.1126/science.309.5731.75 · Cited by 468 · see citing works
The involvement of dopamine in the modulation of sleep and waking
Monti, J. M., & Monti, D. (2007) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2006.08.003 · Cited by 419 · see citing works
Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness
Lewis, L. D., Weiner, V. S., Mukamel, E. A., Donoghue, J., Eskandar, E. N., Madsen, J. R., Anderson, W. S., Hochberg, L. R., Cash, S. S., Brown, E. N., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210907109 · Cited by 387 · see citing works
Self-citationIntracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation
Carlezon, W. A., & Chartoff, E. H. (2007) · Nature Protocols · doi:10.1038/nprot.2007.441 · Cited by 368 · see citing works
The basal ganglia in Parkinson's disease: Current concepts and unexplained observations
Obeso, J. A., Marin, C., Rodriguez-Oroz, C., Blesa, J., Benitez-Temiño, B., Mena-Segovia, J., Rodríguez, M., & Olanow, C. W. (2009) · Annals of Neurology · doi:10.1002/ana.21481 · Cited by 359 · see citing works
Adamantidis, A. R., Tsai, H.-C., Boutrel, B., Zhang, F., Stuber, G. D., Budygin, E. A., Tourino, C., Bonci, A., Deisseroth, K., & de Lecea, L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2246-11.2011 · Cited by 357 · 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
Dahan, L., Astier, B., Vautrelle, N., Urbain, N., Kocsis, B., & Chouvet, G. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301251 · Cited by 289 · see citing works
Vazey, E. M., & Aston-Jones, G. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310025111 · Cited by 279 · see citing works
Miller, J. D., Farber, J., Gatz, P., Roffwarg, H. P., & German, D. C. (1983) · Brain Research · doi:10.1016/0006-8993(83)91101-0 · Cited by 269 · see citing works
Jones, B. E., Bobillier, P., Pin, C., & Jouvet, M. (1973) · Brain Research · doi:10.1016/0006-8993(73)90830-5 · Cited by 246 · see citing works
Leptin regulates the reward value of nutrient
Domingos, A. I., Vaynshteyn, J., Voss, H. U., Ren, X., Gradinaru, V., Zang, F., Deisseroth, K. A., de Araújo, I. E., & Friedman, J. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2977 · Cited by 230 · see citing works
Thalamic 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
Thalamic reticular nucleus induces fast and local modulation of arousal state
Lewis, L. D., Voigts, J., Flores, F. J., Schmitt, L. I., Wilson, M. A., Halassa, M. M., & Brown, E. N. (2015) · eLife · doi:10.7554/elife.08760 · Cited by 204 · see citing works
Self-citationThe neuropharmacology of ADHD drugs in vivo: Insights on efficacy and safety
Heal, D. J., Cheetham, S. C., & Smith, S. L. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.08.020 · Cited by 198 · 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
Self-citationTrulson, M. E., & Preussler, D. W. (1984) · Experimental Neurology · doi:10.1016/s0014-4886(84)90105-5 · Cited by 162 · 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
Self-citationDort, C. J. V., Baghdoyan, H. A., & Lydic, R. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4111-08.2009 · Cited by 138 · see citing works
Excessive Daytime Sleepiness in Patients with Parkinsonʼs Disease
Knie, B., Mitra, M. T., Logishetty, K., & Chaudhuri, K. R. (2011) · CNS Drugs · doi:10.2165/11539720-000000000-00000 · Cited by 132 · see citing works
MacDonald, P. A., & Monchi, O. (2011) · Parkinson s Disease · doi:10.4061/2011/572743 · Cited by 126 · see citing works
Active Emergence from Propofol General Anesthesia Is Induced by Methylphenidate
Chemali, J. J., Dort, C. J. V., Brown, E. N., & Solt, K. (2012) · Anesthesiology · doi:10.1097/aln.0b013e3182518bfc · Cited by 119 · see citing works
Self-citationActivation of D1 Dopamine Receptors Induces Emergence from Isoflurane General Anesthesia
Taylor, N. E., Chemali, J. J., Brown, E. N., & Solt, K. (2012) · Anesthesiology · doi:10.1097/aln.0b013e318278c896 · Cited by 111 · see citing works
Self-citationLee, R., Steffensen, S. C., & Henriksen, S. J. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01757.2001 · Cited by 109 · 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
Luo, T., & Leung, L.-W. S. (2009) · Anesthesiology · doi:10.1097/aln.0b013e3181b061a0 · Cited by 95 · see citing works
Dopamine signaling as a neural correlate of consciousness
Palmiter, R. D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.089 · Cited by 78 · see citing works
Narcolepsy: current treatment options and future approaches
Mamelak, M. (2008) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s484 · Cited by 73 · see citing works
Kenny, J. D., Taylor, N. E., Brown, E. N., & Solt, K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131914 · Cited by 68 · see citing works
Self-citationInvolvement of Tuberomamillary Histaminergic Neurons in Isoflurane Anesthesia
Luo, T., & Leung, L.-W. S. (2011) · Anesthesiology · doi:10.1097/aln.0b013e3182207655 · Cited by 66 · see citing works
Guttmann, E., & Sargant, W. (1937) · BMJ · doi:10.1136/bmj.1.3984.1013 · Cited by 66 · see citing works
Halothane decreases pontine acetylcholine release and increases EEG spindles
Keifer, J. C., Baghdoyan, H. A., Becker, L., et al. (1994) · Neuroreport · doi:10.1097/00001756-199401000-00011 · Cited by 64 · see citing works
Caffeine accelerates recovery from general anesthesia
Wang, Q., Fong, R., Mason, P., Fox, A. P., & Xie, Z. (2013) · Journal of Neurophysiology · doi:10.1152/jn.00792.2013 · Cited by 52 · see citing works
Norepinephrine Infusion into Nucleus Basalis Elicits Microarousal in Desflurane-anesthetized Rats
Pillay, S., Vizuete, J. A., McCallum, J. B., & Hudetz, A. G. (2011) · Anesthesiology · doi:10.1097/aln.0b013e31822c5ee1 · Cited by 51 · see citing works
Swanson, J. M., Wigal, T. L., & Volkow, N. D. (2011) · Psychological Bulletin · doi:10.1037/a0024898 · Cited by 50 · see citing works
The Role of Dopaminergic VTA Neurons in General Anesthesia
Zhou, X., Wang, Y., Chenjing, Z., Wang, M., Zhang, M., Yu, L., & Yan, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138187 · Cited by 49 · see citing works
Benzedrine Sulphate in Clinical Medicine
Bett, W. R. (1946) · Postgraduate Medical Journal · doi:10.1136/pgmj.22.250.205 · Cited by 40 · see citing works
Campbell, A., Villavicencio, A. T., Yeghiayan, S. K., Balikian, R. V., & Baldessarini, R. J. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00777-4 · Cited by 38 · see citing works
Reed, S. J., Plourde, G., Tobin, S. W., & Chapman, C. A. (2012) · British Journal of Anaesthesia · doi:10.1093/bja/aes432 · Cited by 19 · see citing works
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“Reanimation can also be evoked by activation of central pain pathways (Schiff et al., 2007; Brischoux et al., 2009; Anaclet et al., 2014; Roeder et al., 2016; Taylor et al., 2016; Morales and Margolis, 2017).”
Background
- Authors
- Taylor, N. E., Van Dort, C. J., Kenny, J. D., Pei, J., Guidera, J. A., Vlasov, K. Y., Lee, J. T., Boyden, E. S., Brown, E. N., & Solt, K.
- Affiliations
- Harvard University (US)
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114;
- Massachusetts General Hospital (US)
- MIT Media Lab (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-10-24
- Volume
- 113
- Issue
- 45
- Pages
- 12826-12831
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5111696
- OpenAlex
- W2532052289
- Cited by
- 269
- References
- 55
- Citations by year
- 2026: 22 · 2025: 31 · 2024: 43 · 2023: 26 · 2022: 18 · 2021: 40 · 2020: 27 · 2019: 21 · 2018: 27 · 2017: 11 · 2012: 1
- FWCI
- 12.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
- Funders
- HHS | NIH | National Institute of General Medical Sciences (TR01-GM104948, T32-GM07592)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- ventral tegmental area, dopaminergic neurons, optogenetic stimulation, general anesthesia, arousal, wakefulness, consciousness, righting reflex, sleep-wake transition, anesthetic reversal
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