Adaptor protein-3 produces synaptic vesicles that release phasic dopamine.
adaptor protein-3 (AP-3)
phasic dopamine
reinforcement learning
synaptic vesicles
vesicular monoamine transporter 2 (VMAT2)
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
17 10 2023
17 10 2023
Historique:
medline:
23
10
2023
pubmed:
9
10
2023
entrez:
9
10
2023
Statut:
ppublish
Résumé
The burst firing of midbrain dopamine neurons releases a phasic dopamine signal that mediates reinforcement learning. At many synapses, however, high firing rates deplete synaptic vesicles (SVs), resulting in synaptic depression that limits release. What accounts for the increased release of dopamine by stimulation at high frequency? We find that adaptor protein-3 (AP-3) and its coat protein VPS41 promote axonal dopamine release by targeting vesicular monoamine transporter VMAT2 to the axon rather than dendrites. AP-3 and VPS41 also produce SVs that respond preferentially to high-frequency stimulation, independent of their role in axonal polarity. In addition, conditional inactivation of VPS41 in dopamine neurons impairs reinforcement learning, and this involves a defect in the frequency dependence of release rather than the amount of dopamine released. Thus, AP-3 and VPS41 promote the axonal polarity of dopamine release but enable learning by producing a distinct population of SVs tuned specifically to high firing frequency that confers the phasic release of dopamine.
Identifiants
pubmed: 37812725
doi: 10.1073/pnas.2309843120
pmc: PMC10589613
doi:
Substances chimiques
Dopamine
VTD58H1Z2X
Vesicular Monoamine Transport Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2309843120Commentaires et corrections
Type : UpdateOf
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