Dopamine Secretion Is Mediated by Sparse Active Zone-like Release Sites

Cell. 2018 Feb 8;172(4):706-718.e15. doi: 10.1016/j.cell.2018.01.008. Epub 2018 Feb 1.


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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Axons / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism*
  • Dopamine / genetics
  • Dopamine / metabolism*
  • Gene Knockdown Techniques
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Synaptic Transmission / physiology*
  • rab GTP-Binding Proteins


  • ATP-Binding Cassette Transporters
  • Abca4 protein, mouse
  • Bsn protein, mouse
  • Carrier Proteins
  • Erc1 protein, mouse
  • Nerve Tissue Proteins
  • rab GTP-Binding Proteins
  • Dopamine