Fluorescent false neurotransmitters visualize dopamine release from individual presynaptic terminals.
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.
Department of Chemistry, Columbia University, New York, NY 10027, USA.
Niko G
NG
Gubernator
Hui
H
Zhang
Roland G W
RG
Staal
Eugene V
EV
Mosharov
Daniela B
DB
Pereira
Minerva
M
Yue
Vojtech
V
Balsanek
Paul A
PA
Vadola
Bipasha
B
Mukherjee
Robert H
RH
Edwards
David
D
Sulzer
Dalibor
D
Sames
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004558:Electric Stimulation; D005089:Exocytosis; D005456:Fluorescent Dyes; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000378:metabolism*
C541442:8-(2-amino-ethyl)-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-aza-benzo(de)anthracen-10-one; D001551:Benz(a)Anthracenes; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D005456:Fluorescent Dyes; D018377:Neurotransmitter Agents; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D004298:Dopamine