Single-vesicle imaging reveals different transport mechanisms between glutamatergic and GABAergic vesicles

Science. 2016 Feb 26;351(6276):981-4. doi: 10.1126/science.aad8142. Epub 2016 Feb 11.


Synaptic transmission is mediated by the release of neurotransmitters, which involves exo-endocytotic cycling of synaptic vesicles. To maintain synaptic function, synaptic vesicles are refilled with thousands of neurotransmitter molecules within seconds after endocytosis, using the energy provided by an electrochemical proton gradient. However, it is unclear how transmitter molecules carrying different net charges can be efficiently sequestered while maintaining charge neutrality and osmotic balance. We used single-vesicle imaging to monitor pH and electrical gradients and directly showed different uptake mechanisms for glutamate and γ-aminobutyric acid (GABA) operating in parallel. In contrast to glutamate, GABA was exchanged for protons, with no other ions participating in the transport cycle. Thus, only a few components are needed to guarantee reliable vesicle filling with different neurotransmitters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Endocytosis
  • Glutamic Acid / metabolism*
  • Hydrogen-Ion Concentration
  • Mice
  • Mice, Transgenic
  • Molecular Imaging
  • Protons
  • Synaptic Transmission*
  • Synaptic Vesicles / metabolism*
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • Protons
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • Glutamic Acid
  • gamma-Aminobutyric Acid