1/ Mapping synaptic connectivity between individual neurons is extremely laborious. We developed BRISC, a new method that makes it possible to map inputs onto 100s of neurons in the same animal in a matter of weeks! Led by Alex Becalick and @antblot.bsky.social. 🧵 www.biorxiv.org/content/10.1...

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— Petr Znamenskiy (@petrznam.bsky.social) Jul 21, 2025 at 8:58

2/ BRISC uses random molecular barcodes transsynaptically transmitted by rabies viruses to map inputs of many neurons simultaneously, while maintaining single cell resolution. Connections between individual neurons are then identified by matching their barcode sequences.

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— Petr Znamenskiy (@petrznam.bsky.social) Jul 21, 2025 at 8:58

3/ Barcodes are read out from intact tissue sections using in situ sequencing, thus reconstructing presynaptic ensembles of individual starter neurons while preserving spatial information.

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— Petr Znamenskiy (@petrznam.bsky.social) Jul 21, 2025 at 8:58

4/ We apply BRISC in the mouse primary visual cortex, mapping 7,814 putative synaptic connections of 385 starter neurons and identifying layer- and cell-type-specific connectivity rules.

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— Petr Znamenskiy (@petrznam.bsky.social) Jul 21, 2025 at 8:58

\5 Long-range inputs onto single V1 neurons reveal the topography of feedback projections from higher visual areas, which mirrors the retinotopic organisation of the visual cortex.

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— Petr Znamenskiy (@petrznam.bsky.social) Jul 21, 2025 at 8:58

6/ As BRISC does not depend on the availability of transgenic animals, it is readily applicable across brain areas and species to systematically investigate how microcircuit organization varies across the brain and the evolutionary tree. Preprint at www.biorxiv.org/content/10.1...

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— Petr Znamenskiy (@petrznam.bsky.social) Jul 21, 2025 at 8:58