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

Autor: Luján MÁ; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Covey DP; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.; Department of Neuroscience, Lovelace Biomedical Research Institute, Albuquerque, NM, USA., Young-Morrison R; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Zhang L; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Kim A; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Morgado F; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Patel S; Northwestern Center for Psychiatric Neuroscience, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Bass CE; Department of Pharmacology and Toxicology, University at Buffalo, State University of New York, Buffalo, NY, USA., Paladini C; UTSA Neuroscience Institute, University of Texas at San Antonio, San Antonio, TX, USA., Cheer JF; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA. jcheer@som.umaryland.edu.; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. jcheer@som.umaryland.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 20; Vol. 14 (1), pp. 7545. Date of Electronic Publication: 2023 Nov 20.
DOI: 10.1038/s41467-023-43131-3
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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