Activation of ventral tegmental area dopamine neurons produces wakefulness through dopamine D2-like receptors in mice

Brain Structure and Function volume 222, pages2907–2915(2017)Cite this article

Abstract

A growing body of evidence suggests that dopamine plays a role in sleep–wake regulation, but the dopamine-producing brain areas that control sleep–wake states are unclear. In this study, we chemogenetically activated dopamine neurons in the ventral midbrain of mice to examine the role of these neurons in sleep–wake regulation. We found that activation of dopamine neurons in the ventral tegmental area (VTA), but not in the substantia nigra, strongly induced wakefulness, although both cell populations expressed the neuronal activity marker c-Fos after chemogenetic stimulation. Analysis of the pattern of behavioral states revealed that VTA activation increased the duration of wakefulness and decreased the number of wakefulness episodes, indicating that wakefulness was consolidated by VTA activation. The increased wakefulness evoked by VTA activation was completely abolished by pretreatment with the dopamine D2/D3 receptor antagonist raclopride, but not by the D1 receptor antagonist SCH23390. These findings indicate that the activation of VTA dopamine neurons promotes wakefulness via D2/D3 receptors.

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Acknowledgements

Our research was supported by Japan Society for the Promotion of Science Grant 15K18359 (to Y.O.), 26220207/16K18358 (to T.K.), 26640025 (to Y.T.), and 2604762 (to M.L.); a grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Grant-in-Aid for Scientific Research on Innovative Areas “Living in Space”, 16H01629, to M.L.); a CREST grant from the Japan Science and Technology Agency (to M.L.); the World Premier International Research Center Initiative (WPI) from MEXT (to Y.O., T.K., Y.T., Y.C., and M.L.); a grant from the Japan Foundation for Applied Enzymology (to Y.O.) and a grant from The Naito Foundation, Japan (to M.L.).

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    1. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan

      Yo Oishi, Yoshiaki Suzuki, Koji Takahashi, Toshiya Yonezawa, Takeshi Kanda, Yohko Takata, Yoan Cherasse & Michael Lazarus

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    1. Yo Oishi
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    2. Yoshiaki Suzuki
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    3. Koji Takahashi
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    Correspondence to Yo Oishi or Michael Lazarus.

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    Y. Oishi and Y. Suzuki contributed equally to this work.

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    Oishi, Y., Suzuki, Y., Takahashi, K. et al. Activation of ventral tegmental area dopamine neurons produces wakefulness through dopamine D2-like receptors in mice. Brain Struct Funct 222, 2907–2915 (2017). https://doi.org/10.1007/s00429-017-1365-7

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    Keywords

    • Chemogenetics
    • Sleep
    • DAT-Cre mice
    • Midbrain
    • Substantia nigra
    • D1 receptors