Journal
SCIENCE
Volume 324, Issue 5933, Pages 1441-1444Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1172278
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Funding
- The G. Harold and Leila Y. Mathers Charitable Foundation
- Columbia Universitys Research Initiatives in Science and Engineering
- National Institute on Drug Abuse (NIDA)
- National Institute of Mental Health (NIMH)
- Picower and Parkinsons Disease Foundations
- National Alliance for Research on Schizophrenia and Depression
- Michael J. Fox Foundation
- National Parkinson Foundation
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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.
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