Neuron
Volume 95, Issue 5, 30 August 2017, Pages 1074-1088.e7
Journal home page for Neuron

Article
Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT

https://doi.org/10.1016/j.neuron.2017.07.038Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Cell depolarization increases DA vesicular loading prior to release in flies

  • Depolarization-induced SV hyperacidification drives increased DA vesicle loading

  • VGLUT in DA SVs mediates depolarization-induced hyperacidification

  • Depolarization-induced hyperacidification in DA SVs is conserved in mammals

Summary

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.

Keywords

dopamine
glutamate
VGLUT2
synaptic vesicle
pH
neurotransmission
depolarization
vesicle content
presynaptic

Cited by (0)

13

These authors contributed equally

14

Lead Contact