Fluorescent dopamine tracer resolves individual dopaminergic synapses and their activity in the brain

Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):870-5. doi: 10.1073/pnas.1213569110. Epub 2012 Dec 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Axons / metabolism
  • Brain / metabolism*
  • Corpus Striatum / metabolism
  • Dendrites / metabolism
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Fluorescent Dyes* / chemistry
  • Hydrogen-Ion Concentration
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence, Multiphoton
  • Photochemical Processes
  • Presynaptic Terminals / metabolism
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptic Transmission


  • Dopamine Plasma Membrane Transport Proteins
  • Fluorescent Dyes
  • Amphetamine
  • Dopamine