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Dopaminergic Neurons in the Ventral Tegmental–Prelimbic Pathway Promote the Emergence of Rats from Sevoflurane Anesthesia

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Abstract

Dopaminergic neurons in the ventral tegmental area (VTA) play an important role in cognition, emergence from anesthesia, reward, and aversion, and their projection to the cortex is a crucial part of the "bottom-up" ascending activating system. The prelimbic cortex (PrL) is one of the important projection regions of the VTA. However, the roles of dopaminergic neurons in the VTA and the VTADA–PrL pathway under sevoflurane anesthesia in rats remain unclear. In this study, we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist (Chloro-APB) into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats, while injection of a dopamine D1 receptor antagonist (SCH23390) deepened anesthesia. The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA–PrL pathway prolonged the induction time and shortened the emergence time of anesthesia. These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA–PrL pathway facilitates emergence from sevoflurane anesthesia.

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References

  1. Li JM, Liu TA, Dong Y, Kondoh K, Lu ZH. Trans-synaptic neural circuit-tracing with neurotropic viruses. Neurosci Bull 2019, 35: 909–920.

    Article  Google Scholar 

  2. Mashour GA, Hudetz AG. Bottom-up and top-down mechanisms of general anesthetics modulate different dimensions of consciousness. Front Neural Circuits 2017, 11: 44.

    Article  Google Scholar 

  3. Ott T, Nieder A. Dopamine and cognitive control in prefrontal cortex. Trends Cogn Sci 2019, 23: 213–234.

    Article  Google Scholar 

  4. Runegaard AH, Fitzpatrick CM, Woldbye DPD, Andreasen JT, Sørensen AT, Gether U. Modulating dopamine signaling and behavior with chemogenetics: Concepts, progress, and challenges. Pharmacol Rev 2019, 71: 123–156.

    Article  CAS  Google Scholar 

  5. Eban-Rothschild A, Rothschild G, Giardino WJ, Jones JR, de Lecea L. VTA dopaminergic neurons regulate ethologically relevant sleep-wake behaviors. Nat Neurosci 2016, 19: 1356–1366.

    Article  CAS  Google Scholar 

  6. Morales M, Margolis EB. Ventral tegmental area: Cellular heterogeneity, connectivity and behaviour. Nat Rev Neurosci 2017, 18: 73–85.

    Article  CAS  Google Scholar 

  7. Takata Y, Oishi Y, Zhou XZ, Hasegawa E, Takahashi K, Cherasse Y. Sleep and wakefulness are controlled by ventral medial midbrain/Pons GABAergic neurons in mice. J Neurosci 2018, 38: 10080–10092.

    Article  CAS  Google Scholar 

  8. Yu X, Li W, Ma Y, Tossell K, Harris JJ, Harding EC, et al. GABA and glutamate neurons in the VTA regulate sleep and wakefulness. Nat Neurosci 2019, 22: 106–119.

    Article  CAS  Google Scholar 

  9. Yu X, Ba W, Zhao GC, Ma Y, Harding EC, Yin L, et al. Dysfunction of ventral tegmental area GABA neurons causes Mania-like behavior. Mol Psychiatry 2020, https://doi.org/10.1038/s41380-020-0810-9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Qiu G, Wu Y, Yang Z, Li L, Zhu X, Wang Y, et al. Dexmedetomidine activation of dopamine neurons in the ventral tegmental area attenuates the depth of sedation in mice. Anesthesiology 2020, 133: 377–392.

    Article  CAS  Google Scholar 

  11. Taylor NE, Van Dort CJ, Kenny JD, Pei J, Guidera JA, Vlasov KY, et al. Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia. PNAS 2016, 113: 12826–12831.

    Article  CAS  Google Scholar 

  12. Gui H, Liu CX, He HF, Zhang J, Chen H, Zhang Y. Dopaminergic projections from the ventral tegmental area to the nucleus accumbens modulate sevoflurane anesthesia in mice. Front Cell Neurosci 2021, 15: 671473.

  13. Carr DB, Sesack SR. Projections from the rat prefrontal cortex to the ventral tegmental area: Target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons. J Neurosci 2000, 20: 3864–3873.

    Article  CAS  Google Scholar 

  14. Lüscher C, Malenka RC. Drug-evoked synaptic plasticity in addiction: From molecular changes to circuit remodeling. Neuron 2011, 69: 650–663.

    Article  Google Scholar 

  15. Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM, et al. Input-specific control of reward and aversion in the ventral tegmental area. Nature 2012, 491: 212–217.

    Article  CAS  Google Scholar 

  16. Liu D, Tang QQ, Yin C, Song Y, Liu Y, Yang JX, et al. Brain-derived neurotrophic factor-mediated projection-specific regulation of depressive-like and nociceptive behaviors in the mesolimbic reward circuitry. Pain 2018, 159: 175.

    Article  CAS  Google Scholar 

  17. Mininni CJ, Caiafa CF, Zanutto BS, Tseng KY, Lew SE. Putative dopamine neurons in the ventral tegmental area enhance information coding in the prefrontal cortex. Sci Rep 2018, 8: 11740.

    Article  Google Scholar 

  18. Lammel S, Hetzel A, Häckel O, Jones I, Liss B, Roeper J. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron 2008, 57: 760–773.

    Article  CAS  Google Scholar 

  19. Lou TT, Ma J, Wang ZQ, Terakoshi Y, Lee CY, Asher G, et al. Hyper-activation of mPFC underlies specific traumatic stress-induced sleep-wake EEG disturbances. Front Neurosci 2020, 14: 883.

    Article  Google Scholar 

  20. Zhong SJ, Zhang S, Fan XY, Wu Q, Yan LY, Dong J, et al. A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex. Nature 2018, 555: 524–528.

    Article  CAS  Google Scholar 

  21. Lak A, Okun M, Moss MM, Gurnani H, Farrell K, Wells MJ, et al. Dopaminergic and prefrontal basis of learning from sensory confidence and reward value. Neuron 2020, 105: 700-711.e6.

    Article  CAS  Google Scholar 

  22. Zhao SY, Li R, Li HM, Wang S, Zhang XX, Wang D, et al. Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula modulate the anesthetic potency of isoflurane in mice. Neurosci Bull 2021, 37: 934–946.

    Article  CAS  Google Scholar 

  23. Rao XP, Wang J. Neuronal network dissection with neurotropic virus tracing. Neurosci Bull 2020, 36: 199–201.

    Article  Google Scholar 

  24. Cushnie AK, El-Nahal HG, Bohlen MO, May PJ, Basso MA, Grimaldi P, et al. Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation. J Neurosci Methods 2020, 345: 108859.

  25. Melonakos ED, Moody OA, Nikolaeva K, Kato R, Nehs CJ, Solt K. Manipulating neural circuits in anesthesia research. Anesthesiology 2020, 133: 19–30.

    Article  Google Scholar 

  26. Ren SC, Wang YL, Yue FG, Cheng XF, Dang RZ, Qiao QC, et al. The paraventricular thalamus is a critical thalamic area for wakefulness. Science 2018, 362: 429–434.

    Article  CAS  Google Scholar 

  27. Li J, Li H, Wang D, Guo Y, Zhang X, Ran M, et al. Orexin activated emergence from isoflurane anaesthesia involves excitation of ventral tegmental area dopaminergic neurones in rats. Br J Anaesth 2019, 123: 497–505.

    Article  CAS  Google Scholar 

  28. Bao WW, Xu W, Pan GJ, Wang TX, Han Y, Qu WM, et al. Nucleus accumbens neurons expressing dopamine D1 receptors modulate states of consciousness in sevoflurane anesthesia. Curr Biol 2021, 31: 1893-1902.e5.

    Article  CAS  Google Scholar 

  29. Zhang Y, Gui H, Hu L, Li CX, Zhang J, Liang XL. Dopamine D1 receptor in the NAc shell is involved in delayed emergence from isoflurane anesthesia in aged mice. Brain Behav 2021, 11: e01913. https://doi.org/10.1002/brb3.1913.

    Article  PubMed  Google Scholar 

  30. Yanagihara S, Ikebuchi M, Mori C, Tachibana RO, Okanoya K. Arousal state-dependent alterations in neural activity in the zebra finch VTA/SNc. Front Neurosci 2020, 14: 897.

    Article  Google Scholar 

  31. Zhou XL, Wang Y, Zhang CJ, Wang M, Zhang M, Yu LN, et al. The role of dopaminergic VTA neurons in general anesthesia. PLoS One 2015, 10: e0138187. https://doi.org/10.1371/journal.pone.0138187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Solt K, van Dort CJ, Chemali JJ, Taylor NE, Kenny JD, Brown EN. Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia. Anesthesiology 2014, 121: 311–319.

    Article  CAS  Google Scholar 

  33. Tian Y, Chen X, Xu D, Yu J, Lei X. Connectivity within the default mode network mediates the association between chronotype and sleep quality. J Sleep Res 2020, 29: e12948.

  34. Giraldo-Chica M, Rogers BP, Damon SM, Landman BA, Woodward ND. Prefrontal-thalamic anatomical connectivity and executive cognitive function in schizophrenia. Biol Psychiatry 2018, 83: 509–517.

    Article  Google Scholar 

  35. Ong WY, Stohler CS, Herr DR. Role of the prefrontal cortex in pain processing. Mol Neurobiol 2019, 56: 1137–1166.

    Article  CAS  Google Scholar 

  36. Taylor NE, Chemali JJ, Brown EN, Solt K. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia. Anesthesiology 2013, 118: 30–39.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81801366 and 82001453) and the National Key R&D Program of China (2018YFC2001901).

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Correspondence to Yongxin Guo, Weidong Mi or Li Tong.

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Song, Y., Chu, R., Cao, F. et al. Dopaminergic Neurons in the Ventral Tegmental–Prelimbic Pathway Promote the Emergence of Rats from Sevoflurane Anesthesia. Neurosci. Bull. 38, 417–428 (2022). https://doi.org/10.1007/s12264-021-00809-2

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  • DOI: https://doi.org/10.1007/s12264-021-00809-2

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