Dynamic labelling of neural connections in multiple colours by trans-synaptic fluorescence complementation

Lindsey J. Macpherson, Emanuela E. Zaharieva, Patrick J. Kearney, Michael H. Alpert, Tzu Yang Lin, Zeynep Turan, Chi Hon Lee, Marco Gallio*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


Determining the pattern of activity of individual connections within a neural circuit could provide insights into the computational processes that underlie brain function. Here, we develop new strategies to label active synapses by trans-synaptic fluorescence complementation in Drosophila. First, we demonstrate that a synaptobrevin-GRASP chimera functions as a powerful activity-dependent marker for synapses in vivo. Next, we create cyan and yellow variants, achieving activity-dependent, multi-colour fluorescence reconstitution across synapses (X-RASP). Our system allows for the first time retrospective labelling of synapses (rather than whole neurons) based on their activity, in multiple colours, in the same animal. As individual synapses often act as computational units in the brain, our method will promote the design of experiments that are not possible using existing techniques. Moreover, our strategies are easily adaptable to circuit mapping in any genetic system.

Original languageEnglish (US)
Article number10024
JournalNature communications
StatePublished - Dec 4 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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