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Fluorescent False Neurotransmitters Visualize Dopamine Release from Individual Presynaptic Terminals

Neurotransmission in Living Color Neurotransmission involves the release of small molecular neurotransmitters from one neuron to another across a synapse. Gubernator et al. (p. 1441, published online 7 May) introduce a means to observe neurotransmitter release optically, by the design of fluorescent false neurotransmitters, which act as substrates for the synaptic vesicle monoamine transporter. These endogenous monoamine optical tracers enabled visualization of neurotransmitter uptake and release from individual synaptic terminals and were used to evaluate dopamine neurotransmission in the striatum. The fraction of synaptic vesicles that release neurotransmitter per stimulus was frequency dependent, and a frequency-dependent selection of presynaptic terminals was observed. Optical tracking of neurotransmitter release in the brain reveals multiple synaptic populations that depend on brain activity. 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.