Transgenic Targeting of Recombinant Rabies Virus Reveals Monosynaptic Connectivity of Specific Neurons
Name
Weible-2010-Transgenic Targeting of Recombinant Rabies Virus Reveals Monosynaptic Connectivity of Specific Neurons.pdf
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1.34 MB
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Author(s)
Weible, Aldis P.
Schwarcz, Leslie
Wickersham, Ian R.
DeBlander, Leah
Wu, Haiyan
Callaway, Edward M.
Seung, H. Sebastian
Kentros, Clifford G.
Date Issued
December 2010
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Weible, A. P. et al. “Transgenic Targeting of Recombinant Rabies Virus Reveals Monosynaptic Connectivity of Specific Neurons.” Journal of Neuroscience 30.49 (2010) : 16509-16513.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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DOI of Published Version
https://doi.org/10.1523/jneurosci.2442-10.2010
