Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT.
Neuron
; 95(5): 1074-1088.e7, 2017 Aug 30.
Article
em En
| MEDLINE
| ID: mdl-28823729
ABSTRACT
The ability of presynaptic dopamine terminals to tune neurotransmitter release to meet the demands of neuronal activity is critical to neurotransmission. Although vesicle content has been assumed to be static, in vitro data increasingly suggest that cell activity modulates vesicle content. Here, we use a coordinated genetic, pharmacological, and imaging approach in Drosophila to study the presynaptic machinery responsible for these vesicular processes in vivo. We show that cell depolarization increases synaptic vesicle dopamine content prior to release via vesicular hyperacidification. This depolarization-induced hyperacidification is mediated by the vesicular glutamate transporter (VGLUT). Remarkably, both depolarization-induced dopamine vesicle hyperacidification and its dependence on VGLUT2 are seen in ventral midbrain dopamine neurons in the mouse. Together, these data suggest that in response to depolarization, dopamine vesicles utilize a cascade of vesicular transporters to dynamically increase the vesicular pH gradient, thereby increasing dopamine vesicle content.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vesículas Sinápticas
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Dopamina
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Proteína Vesicular 2 de Transporte de Glutamato
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Neuron
Ano de publicação:
2017
Tipo de documento:
Article