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Review
. 2010 May;10(5):763-72.
doi: 10.1517/14712591003796538.

Gene transfer in the nervous system and implications for transsynaptic neuronal tracing

Youngbuhm Huh  1 , Myung S Oh, Pierre Leblanc, Kwang-Soo Kim
Affiliations
Review

Gene transfer in the nervous system and implications for transsynaptic neuronal tracing

Youngbuhm Huh et al. Expert Opin Biol Ther. 2010 May.

Abstract

Importance of the field: Neuronal circuitries are determined by specific synaptic connections and they provide the cellular basis of cognitive processes and behavioral functions. To investigate neuronal circuitries, tracers are typically used to identify the original neurons and their projection targets.

Areas covered in this review: Traditional tracing methods using chemical tracers have major limitations such as non-specificity. In this review, we highlight novel genetic tracing approaches that enable visualization of specific neuronal pathways by introducing cDNA encoding a transsynaptic tracer. In contrast to conventional tracing methods, these genetic approaches use cell-type-specific promoters to express transsynaptic tracers such as wheat germ agglutinin and C-terminal fragment of tetanus toxin, which allows labeling of either the input or output populations and connections of specific neuronal type.

What the reader will gain: Specific neuronal circuit information by these genetic approaches will allow more precise, comprehensive and novel information about individual neural circuits and their function in normal and diseased brains.

Take home message: Using tracer gene transfer, neuronal circuit plasticity after traumatic injury or neurodegenerative diseases can be visualized. Also, this can provide a good marker for evaluation of therapeutic effects of neuroprotective or neurotrophic agents.

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Figures

Figure 1
Figure 1
Schematic diagram indicating the structure of transgene to trace neuronal circuitries. A. A nonspecific promoter drives expression of WGA. B. A nonspecific promoter drives expression of TTC-GFP. C. A nonspecific promoter drives WGA using the Cre-loxP system. D. A cell type specific promoter drives expression of TTC-GFP. E. A cell type specific promoter drives expression of WGA and GFP using the IRES gene. F. A cell type specific promoter drives expression of GFP and WGA-DsRed using the IRES gene. G. A cell type specific promoter drives expression of TTC-AP using the tTA-responsive promoter tetO.
Figure 2
Figure 2
Transneuronal transfer of tracer using conventional and viral tracer gene delivery. A. Conventional tracing. Tracers can be taken up by all the neurons located at the injection sites, resulting in nonspecific labeling of unrelated pathways. B. Viral tracer gene delivery. Tracers can be expressed selectively in specific neurons, resulting in visualization of specific trans-synaptic neuronal pathways.
Figure 2
Figure 2
Transneuronal transfer of tracer using conventional and viral tracer gene delivery. A. Conventional tracing. Tracers can be taken up by all the neurons located at the injection sites, resulting in nonspecific labeling of unrelated pathways. B. Viral tracer gene delivery. Tracers can be expressed selectively in specific neurons, resulting in visualization of specific trans-synaptic neuronal pathways.
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