Freeze-frame imaging of synaptic activity using SynTagMA

Alberto Perez-Alvarez, Brenna C. Fearey, Ryan J. O’Toole, Wei Yang, Ignacio Arganda-Carreras, Paul J. Lamothe-Molina, Benjamien Moeyaert, Manuel A. Mohr, Lauren C. Panzera, Christian Schulze, Eric R. Schreiter, J. Simon Wiegert, Christine E. Gee, Michael B. Hoppa and Thomas G. Oertner ()
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Alberto Perez-Alvarez: University Medical Center Hamburg-Eppendorf
Brenna C. Fearey: University Medical Center Hamburg-Eppendorf
Ryan J. O’Toole: Dartmouth College
Wei Yang: University Medical Center Hamburg-Eppendorf
Ignacio Arganda-Carreras: Basque Foundation for Science
Paul J. Lamothe-Molina: University Medical Center Hamburg-Eppendorf
Benjamien Moeyaert: Janelia Farm Research Campus
Manuel A. Mohr: Janelia Farm Research Campus
Lauren C. Panzera: Dartmouth College
Christian Schulze: University Medical Center Hamburg-Eppendorf
Eric R. Schreiter: Janelia Farm Research Campus
J. Simon Wiegert: University Medical Center Hamburg-Eppendorf
Christine E. Gee: University Medical Center Hamburg-Eppendorf
Michael B. Hoppa: Dartmouth College
Thomas G. Oertner: University Medical Center Hamburg-Eppendorf

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Information within the brain travels from neuron to neuron across billions of synapses. At any given moment, only a small subset of neurons and synapses are active, but finding the active synapses in brain tissue has been a technical challenge. Here we introduce SynTagMA to tag active synapses in a user-defined time window. Upon 395–405 nm illumination, this genetically encoded marker of activity converts from green to red fluorescence if, and only if, it is bound to calcium. Targeted to presynaptic terminals, preSynTagMA allows discrimination between active and silent axons. Targeted to excitatory postsynapses, postSynTagMA creates a snapshot of synapses active just before photoconversion. To analyze large datasets, we show how to identify and track the fluorescence of thousands of individual synapses in an automated fashion. Together, these tools provide an efficient method for repeatedly mapping active neurons and synapses in cell culture, slice preparations, and in vivo during behavior.

Date: 2020
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DOI: 10.1038/s41467-020-16315-4

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