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Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum

Author

Listed:
  • Eduardo F. Gallo

    (Columbia University
    New York State Psychiatric Institute)

  • Jozsef Meszaros

    (New York State Psychiatric Institute)

  • Jeremy D. Sherman

    (Columbia University
    New York State Psychiatric Institute)

  • Muhammad O. Chohan

    (New York State Psychiatric Institute)

  • Eric Teboul

    (Columbia University
    New York State Psychiatric Institute)

  • Claire S. Choi

    (Columbia University
    New York State Psychiatric Institute)

  • Holly Moore

    (Columbia University
    New York State Psychiatric Institute)

  • Jonathan A. Javitch

    (Columbia University
    New York State Psychiatric Institute
    Columbia University)

  • Christoph Kellendonk

    (Columbia University
    New York State Psychiatric Institute
    Columbia University)

Abstract

Dopamine D2 receptors (D2Rs) in the nucleus accumbens (NAc) regulate motivated behavior, but the underlying neurobiological mechanisms remain unresolved. Here, we show that selective upregulation of D2Rs in the indirect pathway of the adult NAc enhances the willingness to work for food. Mechanistic studies in brain slices reveal that D2R upregulation attenuates inhibitory transmission at two main output projections of the indirect pathway, the classical long-range projections to the ventral pallidum (VP), as well as local collaterals to direct pathway medium spiny neurons. In vivo physiology confirms the reduction in indirect pathway inhibitory transmission to the VP, and inhibition of indirect pathway terminals to VP is sufficient to enhance motivation. In contrast, D2R upregulation in the indirect pathway does not disinhibit neuronal activity of the direct pathway in vivo. These data suggest that D2Rs in ventral striatal projection neurons promote motivation by weakening the canonical output to the ventral pallidum.

Suggested Citation

  • Eduardo F. Gallo & Jozsef Meszaros & Jeremy D. Sherman & Muhammad O. Chohan & Eric Teboul & Claire S. Choi & Holly Moore & Jonathan A. Javitch & Christoph Kellendonk, 2018. "Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03272-2
    DOI: 10.1038/s41467-018-03272-2
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    Cited by:

    1. Marie A. Labouesse & Arturo Torres-Herraez & Muhammad O. Chohan & Joseph M. Villarin & Julia Greenwald & Xiaoxiao Sun & Mysarah Zahran & Alice Tang & Sherry Lam & Jeremy Veenstra-VanderWeele & Clay O., 2023. "A non-canonical striatopallidal Go pathway that supports motor control," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Adrien T. Stanley & Michael R. Post & Clay Lacefield & David Sulzer & Maria Concetta Miniaci, 2023. "Norepinephrine release in the cerebellum contributes to aversive learning," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Roman Walle & Anna Petitbon & Giulia R. Fois & Christophe Varin & Enrica Montalban & Lola Hardt & Andrea Contini & Maria Florencia Angelo & Mylène Potier & Rodrigue Ortole & Asma Oummadi & Véronique S, 2024. "Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. 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.

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