Cell
Volume 172, Issue 4, 8 February 2018, Pages 706-718.e15
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Article
Dopamine Secretion Is Mediated by Sparse Active Zone-like Release Sites

https://doi.org/10.1016/j.cell.2018.01.008Get rights and content
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Highlights

  • Striatal dopamine axons contain active zone-like sites with bassoon, RIM, and ELKS

  • RIM is essential for scaffolding and dopamine exocytosis, but ELKS is dispensable

  • These mechanistically specialized sites support a high initial release probability

  • Only ∼30% of dopamine varicosities contain active zone-like sites

Summary

Dopamine controls essential brain functions through volume transmission. Different from fast synaptic transmission, where neurotransmitter release and receptor activation are tightly coupled by an active zone, dopamine transmission is widespread and may not necessitate these organized release sites. Here, we determine whether striatal dopamine secretion employs specialized machinery for release. Using super resolution microscopy, we identified co-clustering of the active zone scaffolding proteins bassoon, RIM and ELKS in ∼30% of dopamine varicosities. Conditional RIM knockout disrupted this scaffold and, unexpectedly, abolished dopamine release, while ELKS knockout had no effect. Optogenetic experiments revealed that dopamine release was fast and had a high release probability, indicating the presence of protein scaffolds for coupling Ca2+ influx to vesicle fusion. Hence, dopamine secretion is mediated by sparse, mechanistically specialized active zone-like release sites. This architecture supports spatially and temporally precise coding for dopamine and provides molecular machinery for regulation.

Keywords

dopamine
exocytosis
active zone
RIM
ELKS
bassoon
striatum
varicosity
volume transmission
superresolution

Cited by (0)

2

Present address: Department of Neuropathology, Charité-Universitätsmedizin, Berlin, Germany

3

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