Departments of Neurology, Columbia University;Departments of Psychiatry and Pharmacology, Columbia University;Department of Chemistry, Columbia University;eMolecules, Inc.;Departments of Neurology and Physiology, University of California School of Medicine, San Francisco;Division of Molecular Therapeutics, New York Psychiatric Institute
Abstract:
The nervous system transmits signals between neurons via neurotransmitter release during synaptic vesicle fusion. 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.Hui Zhang and Niko G. Gubernator contributed equally to this work.Download video file.(112M, mp4)
