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Transgenic targeting of recombinant rabies virus reveals monosynaptic connectivity of specific neurons.
- 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.
- Subjects :
- Animals
Gene Deletion
Gene Expression Regulation, Viral genetics
Green Fluorescent Proteins genetics
Hippocampus cytology
Hippocampus virology
Mice
Mice, Transgenic
Mutation
RNA, Messenger metabolism
Recombination, Genetic
Transgenes physiology
Viral Envelope Proteins metabolism
Neurons physiology
Neurons virology
Rabies virus genetics
Synapses physiology
Viral Envelope Proteins genetics
Subjects
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