Fluorescent false neurotransmitters visualize dopamine release from individual presynaptic terminals

Science. 2009 Jun 12;324(5933):1441-4. doi: 10.1126/science.1172278. Epub 2009 May 7.

Abstract

The nervous system transmits signals between neurons via neurotransmitter release during synaptic vesicle fusion. In order to observe neurotransmitter uptake and release from individual presynaptic terminals directly, we designed fluorescent false neurotransmitters as substrates for the synaptic vesicle monoamine transporter. Using these probes to image dopamine release in the striatum, we made several observations pertinent to synaptic plasticity. We found that the fraction of synaptic vesicles releasing neurotransmitter per stimulus was dependent on the stimulus frequency. A kinetically distinct "reserve" synaptic vesicle population was not observed under these experimental conditions. A frequency-dependent heterogeneity of presynaptic terminals was revealed that was dependent in part on D2 dopamine receptors, indicating a mechanism for frequency-dependent coding of presynaptic selection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benz(a)Anthracenes / metabolism*
  • Cells, Cultured
  • Chromaffin Cells / metabolism*
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Electric Stimulation
  • Exocytosis
  • Fluorescent Dyes
  • Mice
  • Mice, Transgenic
  • Neuronal Plasticity
  • Neurotransmitter Agents / metabolism*
  • Presynaptic Terminals / metabolism*
  • Receptors, Dopamine D2 / metabolism
  • Sulpiride / pharmacology
  • Synaptic Vesicles / metabolism*

Substances

  • 8-(2-amino-ethyl)-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-aza-benzo(de)anthracen-10-one
  • Benz(a)Anthracenes
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Fluorescent Dyes
  • Neurotransmitter Agents
  • Receptors, Dopamine D2
  • Sulpiride
  • Dopamine