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Research ArticleNew Research, Novel Tools and Methods

A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis

Jason S. Snyder, Laura Grigereit, Alexandra Russo, Désirée R. Seib, Michelle Brewer, James Pickel and Heather A. Cameron
eNeuro 12 May 2016, 3 (3) ENEURO.0064-16.2016; DOI: https://doi.org/10.1523/ENEURO.0064-16.2016
Jason S. Snyder
1Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892
3Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada
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Laura Grigereit
1Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892
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Alexandra Russo
1Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892
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Désirée R. Seib
3Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada
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Michelle Brewer
1Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892
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James Pickel
2Transgenic Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, and
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Heather A. Cameron
1Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892
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Abstract

The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis.

  • adult neurogenesis
  • hippocampus
  • olfactory bulb
  • plasticity

Footnotes

  • ↵1 The authors declare no competing financial interests.

  • ↵3 This work was supported by the Intramural Program of the NIH, National Institute of Mental Health, ZIAMH002784 (H.A.C) and NSERC (J.S.S). We thank Dr Lauren Brinster and Rachel Fleishmann, from the Division of Veterinary Resources, NIH, for assistance with pathology.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis
Jason S. Snyder, Laura Grigereit, Alexandra Russo, Désirée R. Seib, Michelle Brewer, James Pickel, Heather A. Cameron
eNeuro 12 May 2016, 3 (3) ENEURO.0064-16.2016; DOI: 10.1523/ENEURO.0064-16.2016

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A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis
Jason S. Snyder, Laura Grigereit, Alexandra Russo, Désirée R. Seib, Michelle Brewer, James Pickel, Heather A. Cameron
eNeuro 12 May 2016, 3 (3) ENEURO.0064-16.2016; DOI: 10.1523/ENEURO.0064-16.2016
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Keywords

  • adult neurogenesis
  • hippocampus
  • olfactory bulb
  • Plasticity

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