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Nat Commun. 2017 Oct 31;8(1):1229. doi: 10.1038/s41467-017-01335-4.

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

Author information

1
Università Vita-Salute San Raffaele, Milan, 20132, Italy.
2
Neurobiology of Learning Unit, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milan, 20132, Italy.
3
Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milan, 20132, Italy.
4
Department of Physiology, Institute of Basal Medical Sciences, University of Oslo, Oslo, 0315, Norway.
5
Dipartimento Testa-Collo, San Paolo Hospital, University of Milan, Milan, 20122, Italy.
6
Keires AG, Basel, CH 4051, Switzerland.
7
Università Vita-Salute San Raffaele, Milan, 20132, Italy. malgaroli.antonio@unisr.it.
8
Neurobiology of Learning Unit, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milan, 20132, Italy. malgaroli.antonio@unisr.it.

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.

PMID:
29089485
PMCID:
PMC5663910
DOI:
10.1038/s41467-017-01335-4
[Indexed for MEDLINE]
Free PMC Article

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