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

Cell | 2018

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.

Pubmed ID: 29398114 RIS Download

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: P30 NS072030
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS083898
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS103484
  • Agency: NICHD NIH HHS, United States
    Id: U54 HD090255

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This is a list of tools and resources that we have found mentioned in this publication.


Anti-Tyrosine hydroxylase (antibody)

RRID:AB_2619897

This polyclonal targets Tyrosine hydroxylase

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R809 (antibody)

RRID:AB_2617051

This polyclonal targets RIM1 central domains

View all literature mentions

Anti-SNAP 25 (antibody)

RRID:AB_887790

This polyclonal targets SNAP 25

View all literature mentions

Bassoon, mAb (SAP7F407) (antibody)

RRID:AB_11181058

This unknown targets Bassoon mAb (SAP7F407)

View all literature mentions

Anti-Synaptobrevin 2 (antibody)

RRID:AB_887810

This polyclonal targets Synaptobrevin 2

View all literature mentions

Anti-Synaptophysin 1 (antibody)

RRID:AB_887824

This monoclonal targets Synaptophysin 1

View all literature mentions

Anti-Tyrosine Hydroxylase Antibody (antibody)

RRID:AB_390204

This polyclonal targets Tyrosine Hydroxylase

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Anti-Munc 13-1 (antibody)

RRID:AB_887733

This polyclonal targets Munc 13-1

View all literature mentions

Anti-Bassoon (antibody)

RRID:AB_2290619

This polyclonal targets Bassoon

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B6.SJL-Slc6a3tm1.1(cre)Bkmn/J (organism)

RRID:IMSR_JAX:006660

Mus musculus with name B6.SJL-Slc6a3tm1.1(cre)Bkmn/J from IMSR.

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B6;129S-Slc17a7tm1.1(cre)Hze/J (organism)

RRID:IMSR_JAX:023527

Mus musculus with name B6;129S-Slc17a7tm1.1(cre)Hze/J from IMSR.

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STOCK Rims1tm3Sud/J (organism)

RRID:IMSR_JAX:015832

Mus musculus with name STOCK Rims1tm3Sud/J from IMSR.

View all literature mentions

STOCK Rims2tm1.1Sud/J (organism)

RRID:IMSR_JAX:015833

Mus musculus with name STOCK Rims2tm1.1Sud/J from IMSR.

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STOCK Erc2tm1.2Sud/J (organism)

RRID:IMSR_JAX:015831

Mus musculus with name STOCK Erc2tm1.2Sud/J from IMSR.

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STOCK Erc1tm2.1Sud/J (organism)

RRID:IMSR_JAX:015830

Mus musculus with name STOCK Erc1tm2.1Sud/J from IMSR.

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B6;129S-Gt(ROSA)26Sortm34.1(CAG-Syp/tdTomato)Hze/J (organism)

RRID:IMSR_JAX:012570

Mus musculus with name B6;129S-Gt(ROSA)26Sortm34.1(CAG-Syp/tdTomato)Hze/J from IMSR.

View all literature mentions

Anti-Tyrosine Hydroxylase Antibody (antibody)

RRID:AB_390204

This polyclonal targets Tyrosine Hydroxylase

View all literature mentions

Bassoon, mAb (SAP7F407) (antibody)

RRID:AB_11181058

This unknown targets Bassoon mAb (SAP7F407)

View all literature mentions

Anti-Bassoon (antibody)

RRID:AB_2290619

This polyclonal targets Bassoon

View all literature mentions

R809 (antibody)

RRID:AB_2617051

This polyclonal targets RIM1 central domains

View all literature mentions

Anti-Munc 13-1 (antibody)

RRID:AB_887733

This polyclonal targets Munc 13-1

View all literature mentions

B6;129S-Slc17a7tm1.1(cre)Hze/J (organism)

RRID:IMSR_JAX:023527

Mus musculus with name B6;129S-Slc17a7tm1.1(cre)Hze/J from IMSR.

View all literature mentions

B6;129S-Gt(ROSA)26Sortm34.1(CAG-Syp/tdTomato)Hze/J (organism)

RRID:IMSR_JAX:012570

Mus musculus with name B6;129S-Gt(ROSA)26Sortm34.1(CAG-Syp/tdTomato)Hze/J from IMSR.

View all literature mentions

STOCK Erc2tm1.2Sud/J (organism)

RRID:IMSR_JAX:015831

Mus musculus with name STOCK Erc2tm1.2Sud/J from IMSR.

View all literature mentions

STOCK Erc1tm2.1Sud/J (organism)

RRID:IMSR_JAX:015830

Mus musculus with name STOCK Erc1tm2.1Sud/J from IMSR.

View all literature mentions

STOCK Rims2tm1.1Sud/J (organism)

RRID:IMSR_JAX:015833

Mus musculus with name STOCK Rims2tm1.1Sud/J from IMSR.

View all literature mentions

STOCK Rims1tm3Sud/J (organism)

RRID:IMSR_JAX:015832

Mus musculus with name STOCK Rims1tm3Sud/J from IMSR.

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B6.SJL-Slc6a3tm1.1(cre)Bkmn/J (organism)

RRID:IMSR_JAX:006660

Mus musculus with name B6.SJL-Slc6a3tm1.1(cre)Bkmn/J from IMSR.

View all literature mentions

Anti-SNAP 25 (antibody)

RRID:AB_887790

This polyclonal targets SNAP 25

View all literature mentions

Anti-Synaptophysin 1 (antibody)

RRID:AB_887824

This monoclonal targets Synaptophysin 1

View all literature mentions

Anti-Synaptobrevin 2 (antibody)

RRID:AB_887810

This polyclonal targets Synaptobrevin 2

View all literature mentions

Anti-Tyrosine hydroxylase (antibody)

RRID:AB_2619897

This polyclonal targets Tyrosine hydroxylase

View all literature mentions