Journal
NATURE METHODS
Volume 17, Issue 12, Pages 1254-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41592-020-00989-1
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Funding
- Dorothy Hodgkin Fellowship from the Royal Society [DH120072]
- ERC [211089, 649111]
- MRC [MC-U105188491]
- NIH [2P40OD010949]
- Royal Society [DH120072] Funding Source: Royal Society
- European Research Council (ERC) [211089, 649111] Funding Source: European Research Council (ERC)
- MRC [MC_U105188491] Funding Source: UKRI
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Animal behavior is encoded in neuronal circuits in the brain. To elucidate the function of these circuits, it is necessary to identify, record from and manipulate networks of connected neurons. Here we present BAcTrace (Botulinum-Activated Tracer), a genetically encoded, retrograde, transsynaptic labeling system. BAcTrace is based on Clostridium botulinum neurotoxin A, Botox, which we engineered to travel retrogradely between neurons to activate an otherwise silent transcription factor. We validated BAcTrace at three neuronal connections in the Drosophila olfactory system. We show that BAcTrace-mediated labeling allows electrophysiological recording of connected neurons. Finally, in a challenging circuit with highly divergent connections, BAcTrace correctly identified 12 of 16 connections that were previously observed by electron microscopy. BAcTrace is a predominantly retrograde tracing tool for connectomic analyses in Drosophila.
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