Cre-Dependent Anterograde Transsynaptic Labeling and Functional Imaging in Zebrafish Using VSV With Reduced Cytotoxicity

dc.contributor.authorKler, Stanislaven
dc.contributor.authorMa, Manxiuen
dc.contributor.authorNarayan, Sujathaen
dc.contributor.authorAhrens, Misha Benjaminen
dc.contributor.authorPan, Yuchin Alberten
dc.date.accessioned2021-10-07T17:37:33Zen
dc.date.available2021-10-07T17:37:33Zen
dc.date.issued2021-10-06en
dc.description.abstractThe small size and translucency of larval zebrafish (Danio rerio) have made it a unique experimental system to investigate whole-brain neural circuit structure and function. Still, the connectivity patterns between most neuronal types remain mostly unknown. This gap in knowledge underscores the critical need for effective neural circuit mapping tools, especially ones that can integrate structural and functional analyses. To address this, we previously developed a vesicular stomatitis virus (VSV) based approach called Tracer with Restricted Anterograde Spread (TRAS). TRAS utilizes lentivirus to complement replication-incompetent VSV (VSVΔG) to allow restricted (monosynaptic) anterograde labeling from projection neurons to their target cells in the brain. Here, we report the second generation of TRAS (TRAS-M51R), which utilizes a mutant variant of VSVΔG [VSV(M51R)ΔG] with reduced cytotoxicity. Within the primary visual pathway, we found that TRAS-M51R significantly improved long-term viability of transsynaptic labeling (compared to TRAS) while maintaining anterograde spread activity. By using Cre-expressing VSV(M51R)ΔG, TRAS-M51R could selectively label excitatory (vglut2a positive) and inhibitory (gad1b positive) retinorecipient neurons. We further show that these labeled excitatory and inhibitory retinorecipient neurons retained neuronal excitability upon visual stimulation at 5–8 days post fertilization (2–5 days post-infection). Together, these findings show that TRAS-M51R is suitable for neural circuit studies that integrate structural connectivity, cell-type identity, and neurophysiology.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fnana.2021.758350en
dc.identifier.eissn1662-5129en
dc.identifier.urihttp://hdl.handle.net/10919/105200en
dc.identifier.volume15en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjecttranssynapticen
dc.subjectzebrafishen
dc.subjectVSV (vesicular stomatitis virus)en
dc.subjectTRAS-M51Ren
dc.subjectbrain mappingen
dc.subjectviral tracingen
dc.titleCre-Dependent Anterograde Transsynaptic Labeling and Functional Imaging in Zebrafish Using VSV With Reduced Cytotoxicityen
dc.title.serialFrontiers in Neuroanatomyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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