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

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....

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Vydané v:Cell Ročník 172; číslo 4; s. 706
Hlavní autori: Liu, Changliang, Kershberg, Lauren, Wang, Jiexin, Schneeberger, Shirin, Kaeser, Pascal S
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 08.02.2018
Predmet:
Animals
ATP-Binding Cassette Transporters - genetics
ATP-Binding Cassette Transporters - metabolism
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
rab GTP-Binding Proteins
Synaptic Transmission - physiology
striatum
RIM
active zone
superresolution
varicosity
volume transmission
exocytosis
bassoon
dopamine
ELKS
ISSN:1097-4172, 1097-4172
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Popis
Shrnutí: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 Ca 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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2018.01.008