Functional mapping of brain synapses by the enriching activity-marker SynaptoZip

Mattia Ferro, Jacopo Lamanna, Maddalena Ripamonti, Gabriella Racchetti, Alessandro Arena, Sara Spadini, Giovanni Montesano, Riccardo Cortese, Vincenzo Zimarino and Antonio Malgaroli ()
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Mattia Ferro: Università Vita-Salute San Raffaele
Jacopo Lamanna: Università Vita-Salute San Raffaele
Maddalena Ripamonti: Università Vita-Salute San Raffaele
Gabriella Racchetti: Università Vita-Salute San Raffaele
Alessandro Arena: Università Vita-Salute San Raffaele
Sara Spadini: Università Vita-Salute San Raffaele
Giovanni Montesano: Università Vita-Salute San Raffaele
Riccardo Cortese: Keires AG
Vincenzo Zimarino: Scientific Institute Ospedale San Raffaele
Antonio Malgaroli: Università Vita-Salute San Raffaele

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Ideally, elucidating the role of specific brain circuits in animal behavior would require the ability to measure activity at all involved synapses, possibly with unrestricted field of view, thus even at those boutons deeply located into the brain. Here, we introduce and validate an efficient scheme reporting synaptic vesicle cycling in vivo. This is based on SynaptoZip, a genetically encoded molecule deploying in the vesicular lumen a bait moiety designed to capture upon exocytosis a labeled alien peptide, Synbond. The resulting signal is cumulative and stores the number of cycling events occurring at individual synapses. Since this functional signal is enduring and measurable both online and ex post, SynaptoZip provides a unique method for the analysis of the history of synaptic activity in regions several millimeters below the brain surface. We show its broad applicability by reporting stimulus-evoked and spontaneous circuit activity in wide cortical fields, in anesthetized and freely moving animals.

Date: 2017
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DOI: 10.1038/s41467-017-01335-4

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