title: Fluorescent dopamine tracer resolves individual dopaminergic synapses and their activity in the brain.
abstract: We recently introduced fluorescent false neurotransmitters (FFNs) as optical tracers that enable the visualization of neurotransmitter release at individual presynaptic terminals. Here, we describe a pH-responsive FFN probe, FFN102, which as a polar dopamine transporter substrate selectively labels dopamine cell bodies and dendrites in ventral midbrain and dopaminergic synaptic terminals in dorsal striatum. FFN102 exhibits greater fluorescence emission in neutral than acidic environments, and thus affords a means to optically measure evoked release of synaptic vesicle content into the extracellular space. Simultaneously, FFN102 allows the measurement of individual synaptic terminal activity by following fluorescence loss upon stimulation. Thus, FFN102 enables not only the identification of dopamine cells and their processes in brain tissue, but also the optical measurement of functional parameters including dopamine transporter activity and dopamine release at the level of individual synapses. As such, the development of FFN102 demonstrates that, by bringing together organic chemistry and neuroscience, molecular entities can be generated that match the endogenous transmitters in selectivity and distribution, allowing for the study of both the microanatomy and functional plasticity of the normal and diseased nervous system.
authors.affiliation: Department of Chemistry, Columbia University, New York, NY 10027, USA.
authors.forename: Pamela C
authors.initials: PC
authors.lastname: Rodriguez
authors.forename: Daniela B
authors.initials: DB
authors.lastname: Pereira
authors.forename: Anders
authors.initials: A
authors.lastname: Borgkvist
authors.forename: Minerva Y
authors.initials: MY
authors.lastname: Wong
authors.forename: Candace
authors.initials: C
authors.lastname: Barnard
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sonders
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Dalibor
authors.initials: D
authors.lastname: Sames
authors.forename: David
authors.initials: D
authors.lastname: Sulzer
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton; D055668:Photochemical Processes; D017729:Presynaptic Terminals / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005456:Fluorescent Dyes; D000661:Amphetamine; D004298:Dopamine