Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia
Name
Taylor-2016-Optogenetic activation of dopamine.pdf
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Author(s)
Taylor, Norman
Van Dort, Christa Joy
Kenny, Jonathan Dillion
Pei, JunZhu
Guidera, Jennifer
Vlasov, Ksenia
Lee, Justin
Boyden, Edward
Brown, Emery Neal
Solt, Ken
Date Issued
October 2016
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Taylor, Norman E.; Van Dort, Christa J.; Kenny, Jonathan D.; Pei, JunZhu; Guidera, Jennifer A.; Vlasov, Ksenia Y.; Lee, Justin T.; Boyden, Edward S.; Brown, Emery N. and Solt, Ken. “Optogenetic Activation of Dopamine Neurons in the Ventral Tegmental Area Induces Reanimation from General Anesthesia.” Proceedings of the National Academy of Sciences 113, no. 45 (October 2016): 12826–12831. © 2016 National Academy of Sciences
Version
Final published version
Abstract
Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2− group; n = 5). VTA optical stimulation in ChR2− mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Media Laboratory
McGovern Institute for Brain Research at MIT
Picower Institute for Learning and Memory
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1614340113
