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Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction

Author

Listed:
  • Miguel Á. Luján

    (University of Maryland School of Medicine)

  • Dan P. Covey

    (University of Maryland School of Medicine
    Lovelace Biomedical Research Institute)

  • Reana Young-Morrison

    (University of Maryland School of Medicine)

  • LanYuan Zhang

    (University of Maryland School of Medicine)

  • Andrew Kim

    (University of Maryland School of Medicine)

  • Fiorella Morgado

    (University of Maryland School of Medicine)

  • Sachin Patel

    (Northwestern University Feinberg School of Medicine)

  • Caroline E. Bass

    (University at Buffalo, State University of New York)

  • Carlos Paladini

    (University of Texas at San Antonio)

  • Joseph F. Cheer

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

Abstract

Brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) shape motivated behavior and nucleus accumbens (NAc) dopamine release. However, it is not clear whether mobilization of 2-AG specifically from midbrain dopamine neurons is necessary for dopaminergic responses to external stimuli predicting forthcoming reward. Here, we use a viral-genetic strategy to prevent the expression of the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) from ventral tegmental area (VTA) dopamine cells in adult mice. We find that DGLα deletion from VTA dopamine neurons prevents depolarization-induced suppression of excitation (DSE), a form of 2-AG-mediated synaptic plasticity, in dopamine neurons. DGLα deletion also decreases effortful, cue-driven reward-seeking but has no effect on non-cued or low-effort operant tasks and other behaviors. Moreover, dopamine recording in the NAc reveals that deletion of DGLα impairs the transfer of accumbal dopamine signaling from a reward to its earliest predictors. These results demonstrate that 2-AG mobilization from VTA dopamine neurons is a necessary step for the generation of dopamine-based predictive associations that are required to direct and energize reward-oriented behavior.

Suggested Citation

  • Miguel Á. Luján & Dan P. Covey & Reana Young-Morrison & LanYuan Zhang & Andrew Kim & Fiorella Morgado & Sachin Patel & Caroline E. Bass & Carlos Paladini & Joseph F. Cheer, 2023. "Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43131-3
    DOI: 10.1038/s41467-023-43131-3
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