Language

English

Publication Date

2-1-2024

Journal

Nature Neuroscience

DOI

10.1038/s41593-023-01545-8

PMID

38212587

PMCID

PMC10849964

PubMedCentral® Posted Date

1-11-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Rabies-virus-based monosynaptic tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Viral spread requires expression of both deleted viral genes in trans in postsynaptic source cells. Suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imaging in vivo indicated that over 90% of both presynaptic and source cells survived for the full 12-week course of imaging. Ex vivo whole-cell recordings at 5 weeks postinfection showed that the second-generation system perturbs input and source cells much less than the first-generation system. Finally, two-photon calcium imaging of labeled networks of visual cortex neurons showed that their visual response properties appeared normal for 10 weeks, the longest we followed them.

Keywords

Rabies virus, Neurons, Virus Replication

Comments

This article has been corrected. See Nat Neurosci. 2024 Jan 24;27(2):385.

Published Open-Access

yes

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