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Transgenic targeting of recombinant rabies virus reveals monosynaptic connectivity of specific neurons.

Authors :
Weible AP
Schwarcz L
Wickersham IR
Deblander L
Wu H
Callaway EM
Seung HS
Kentros CG
Source :
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2010 Dec 08; Vol. 30 (49), pp. 16509-13.
Publication Year :
2010

Abstract

Understanding how neural circuits work requires a detailed knowledge of cellular-level connectivity. Our current understanding of neural circuitry is limited by the constraints of existing tools for transsynaptic tracing. Some of the most intractable problems are a lack of cellular specificity of uptake, transport across multiple synaptic steps conflating direct and indirect inputs, and poor labeling of minor inputs. We used a novel combination of transgenic mouse technology and a recently developed tracing system based on rabies virus (Wickersham et al., 2007a,b) to overcome all three constraints. Because the virus requires transgene expression for both initial infection and subsequent retrograde transsynaptic infection, we created several lines of mice that express these genes in defined cell types using the tetracycline-dependent transactivator system (Mansuy and Bujard, 2000). Fluorescent labeling from viral replication is thereby restricted to defined neuronal cell types and their direct monosynaptic inputs. Because viral replication does not depend on transgene expression, it provides robust amplification of signal in presynaptic neurons regardless of input strength. We injected virus into transgenic crosses expressing the viral transgenes in specific cell types of the hippocampus formation to demonstrate cell-specific infection and monosynaptic retrograde transport of virus, which strongly labels even minor inputs. Such neuron-specific transgenic complementation of recombinant rabies virus holds great promise for obtaining cellular-resolution wiring diagrams of the mammalian CNS.

Details

Language :
English
ISSN :
1529-2401
Volume :
30
Issue :
49
Database :
MEDLINE
Journal :
The Journal of neuroscience : the official journal of the Society for Neuroscience
Publication Type :
Academic Journal
Accession number :
21147990
Full Text :
https://doi.org/10.1523/JNEUROSCI.2442-10.2010