Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 Nov 2023
20 Nov 2023
Historique:
received:
31
01
2023
accepted:
01
11
2023
medline:
27
11
2023
pubmed:
21
11
2023
entrez:
21
11
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37985770
doi: 10.1038/s41467-023-43131-3
pii: 10.1038/s41467-023-43131-3
pmc: PMC10662422
doi:
Substances chimiques
Dopamine
VTD58H1Z2X
Endocannabinoids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7545Subventions
Organisme : NIDA NIH HHS
ID : F32 DA041827
Pays : United States
Organisme : NIDA NIH HHS
ID : R00 DA047432
Pays : United States
Organisme : NIDA NIH HHS
ID : K99 DA047432
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA022340
Pays : United States
Informations de copyright
© 2023. The Author(s).
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