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Genetic manipulation of specific neural circuits by use of a viral vector system

  • Translational Neurosciences - Review Article
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Abstract

To understand the mechanisms underlying higher brain functions, we need to analyze the roles of specific neuronal pathways or cell types forming the complex neural networks. In the neuroscience field, the transgenic approach has provided a useful gene engineering tool for experimental studies of neural functions. The conventional transgenic technique requires the appropriate promoter regions that drive a neuronal type-specific gene expression, but the promoter sequences specifically functioning in each neuronal type are limited. Previously, we developed novel types of lentiviral vectors showing high efficiency of retrograde gene transfer in the central nervous system, termed highly efficient retrograde gene transfer (HiRet) vector and neuron-specific retrograde gene transfer (NeuRet) vector. The HiRet and NeuRet vectors enable genetical manipulation of specific neural pathways in diverse model animals in combination with conditional cell targeting, synaptic transmission silencing, and gene expression systems. These newly developed vectors provide powerful experimental strategies to investigate, more precisely, the machineries exerting various neural functions. In this review, we give an outline of the HiRet and NeuRet vectors and describe recent representative applications of these viral vectors for studies on neural circuits.

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Acknowledgements

This work was supported by a grant-in-aid for Scientific Research on Innovative Areas “Adaptive Circuit Shift” (26112002) from the Ministry of Education, Science, Sports, and Culture of Japan. We thank Dr. A. Nambu, T. Isa, M. Takada, and K. Kaibuchi for valuable discussions; Dr. Ira Pastan for providing the recombinant immunotoxin; and St. Jude Children’s Research Hospital (Dr. A. Nienhuis) and George Washington University for providing the HIV-1-based vector system.

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  1. Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki, 444-8585, Japan

    Kenta Kobayashi

  2. SOKENDAI (The Graduate University for Advanced Studies), Hayama, 240-0193, Japan

    Kenta Kobayashi

  3. Department of Molecular Genetics, Institute of Biomedical Sciences, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan

    Shigeki Kato & Kazuto Kobayashi

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  1. Kenta Kobayashi
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Correspondence to Kenta Kobayashi.

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Kobayashi, K., Kato, S. & Kobayashi, K. Genetic manipulation of specific neural circuits by use of a viral vector system. J Neural Transm 125, 67–75 (2018). https://doi.org/10.1007/s00702-016-1674-7

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