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Dopamine D2 receptors in discrimination learning and spine enlargement

Author

Listed:
  • Yusuke Iino

    (The University of Tokyo
    The University of Tokyo)

  • Takeshi Sawada

    (The University of Tokyo
    The University of Tokyo)

  • Kenji Yamaguchi

    (The University of Tokyo
    The University of Tokyo)

  • Mio Tajiri

    (The University of Tokyo
    The University of Tokyo)

  • Shin Ishii

    (The University of Tokyo
    Kyoto University)

  • Haruo Kasai

    (The University of Tokyo
    The University of Tokyo)

  • Sho Yagishita

    (The University of Tokyo
    The University of Tokyo)

Abstract

Dopamine D2 receptors (D2Rs) are densely expressed in the striatum and have been linked to neuropsychiatric disorders such as schizophrenia1,2. High-affinity binding of dopamine suggests that D2Rs detect transient reductions in dopamine concentration (the dopamine dip) during punishment learning3–5. However, the nature and cellular basis of D2R-dependent behaviour are unclear. Here we show that tone reward conditioning induces marked stimulus generalization in a manner that depends on dopamine D1 receptors (D1Rs) in the nucleus accumbens (NAc) of mice, and that discrimination learning refines the conditioning using a dopamine dip. In NAc slices, a narrow dopamine dip (as short as 0.4 s) was detected by D2Rs to disinhibit adenosine A2A receptor (A2AR)-mediated enlargement of dendritic spines in D2R-expressing spiny projection neurons (D2-SPNs). Plasticity-related signalling by Ca2+/calmodulin-dependent protein kinase II and A2ARs in the NAc was required for discrimination learning. By contrast, extinction learning did not involve dopamine dips or D2-SPNs. Treatment with methamphetamine, which dysregulates dopamine signalling, impaired discrimination learning and spine enlargement, and these impairments were reversed by a D2R antagonist. Our data show that D2Rs refine the generalized reward learning mediated by D1Rs.

Suggested Citation

  • Yusuke Iino & Takeshi Sawada & Kenji Yamaguchi & Mio Tajiri & Shin Ishii & Haruo Kasai & Sho Yagishita, 2020. "Dopamine D2 receptors in discrimination learning and spine enlargement," Nature, Nature, vol. 579(7800), pages 555-560, March.
  • Handle: RePEc:nat:nature:v:579:y:2020:i:7800:d:10.1038_s41586-020-2115-1
    DOI: 10.1038/s41586-020-2115-1
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    Citations

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    Cited by:

    1. Marie A. Labouesse & Maria Wilhelm & Zacharoula Kagiampaki & Andrew G. Yee & Raphaelle Denis & Masaya Harada & Andrea Gresch & Alina-Măriuca Marinescu & Kanako Otomo & Sebastiano Curreli & Laia Serrat, 2024. "A chemogenetic approach for dopamine imaging with tunable sensitivity," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    2. Susanne Prokop & Péter Ábrányi-Balogh & Benjámin Barti & Márton Vámosi & Miklós Zöldi & László Barna & Gabriella M. Urbán & András Dávid Tóth & Barna Dudok & Attila Egyed & Hui Deng & Gian Marco Leggi, 2021. "PharmacoSTORM nanoscale pharmacology reveals cariprazine binding on Islands of Calleja granule cells," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    3. Yosuke Yawata & Yu Shikano & Jun Ogasawara & Kenichi Makino & Tetsuhiko Kashima & Keiko Ihara & Airi Yoshimoto & Shota Morikawa & Sho Yagishita & Kenji F. Tanaka & Yuji Ikegaya, 2023. "Mesolimbic dopamine release precedes actively sought aversive stimuli in mice," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Allen P. F. Chen & Jeffrey M. Malgady & Lu Chen & Kaiyo W. Shi & Eileen Cheng & Joshua L. Plotkin & Shaoyu Ge & Qiaojie Xiong, 2022. "Nigrostriatal dopamine pathway regulates auditory discrimination behavior," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Koustav Roy & Xuzhao Zhou & Rintaro Otani & Ping-Chuan Yuan & Shuji Ioka & Kaspar E. Vogt & Tamae Kondo & Nouran H. T. Farag & Haruto Ijiri & Zhaofa Wu & Youhei Chitose & Mao Amezawa & David S. Uygun , 2024. "Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A2A receptors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Tadaaki Nishioka & Suthinee Attachaipanich & Kosuke Hamaguchi & Michael Lazarus & Alban Kerchove d’Exaerde & Tom Macpherson & Takatoshi Hikida, 2023. "Error-related signaling in nucleus accumbens D2 receptor-expressing neurons guides inhibition-based choice behavior in mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Allen P. F. Chen & Lu Chen & Kaiyo W. Shi & Eileen Cheng & Shaoyu Ge & Qiaojie Xiong, 2023. "Nigrostriatal dopamine modulates the striatal-amygdala pathway in auditory fear conditioning," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Huiling Yu & Liping Chen & Huiyang Lei & Guilin Pi & Rui Xiong & Tao Jiang & Dongqin Wu & Fei Sun & Yang Gao & Yuanhao Li & Wenju Peng & Bingyu Huang & Guoda Song & Xin Wang & Jingru Lv & Zetao Jin & , 2022. "Infralimbic medial prefrontal cortex signalling to calbindin 1 positive neurons in posterior basolateral amygdala suppresses anxiety- and depression-like behaviours," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Kuikui Zhou & Hua Xu & Shanshan Lu & Shaolei Jiang & Guoqiang Hou & Xiaofei Deng & Miao He & Yingjie Zhu, 2022. "Reward and aversion processing by input-defined parallel nucleus accumbens circuits in mice," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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