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Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT.

Neuron | Aug 30, 2017

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.

Pubmed ID: 28823729 RIS Download

Mesh terms: Animals | Animals, Genetically Modified | Dextroamphetamine | Dopamine | Drosophila | Drosophila Proteins | Hydrogen-Ion Concentration | Locomotion | Mesencephalon | Mice | Neurons | Presynaptic Terminals | Synaptic Vesicles | Vesicular Glutamate Transport Protein 2

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Associated grants

  • Agency: NIDA NIH HHS, Id: P01 DA010154
  • Agency: NIGMS NIH HHS, Id: T32 GM007628
  • Agency: NIMH NIH HHS, Id: R01 MH108186
  • Agency: NIEHS NIH HHS, Id: R01 ES015747
  • Agency: NIMH NIH HHS, Id: R01 MH086545
  • Agency: NINDS NIH HHS, Id: R21 NS075572
  • Agency: NIA NIH HHS, Id: P50 AG008702
  • Agency: NIMH NIH HHS, Id: R01 MH107390
  • Agency: NINDS NIH HHS, Id: R01 NS075222
  • Agency: NIDA NIH HHS, Id: K05 DA022413
  • Agency: NIDA NIH HHS, Id: R01 DA038966
  • Agency: NIMH NIH HHS, Id: R01 MH076900
  • Agency: NIDA NIH HHS, Id: P01 DA012408
  • Agency: NIEHS NIH HHS, Id: P01 ES016732
  • Agency: NIDA NIH HHS, Id: K08 DA031241
  • Agency: NIDA NIH HHS, Id: R01 DA007418
  • Agency: NIDA NIH HHS, Id: R21 DA040443

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