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TrkB kinase is required for recovery, but not loss, of cortical responses following monocular deprivation

Nature Neuroscience volume 11, pages 497–504 (2008)Cite this article

Abstract

Changes in visual cortical responses that are induced by monocular visual deprivation are a widely studied example of competitive, experience-dependent neural plasticity. It has been thought that the deprived-eye pathway will fail to compete against the open-eye pathway for limited amounts of brain-derived neurotrophic factor, which acts on TrkB and is needed to sustain effective synaptic connections. We tested this model by using a chemical-genetic approach in mice to inhibit TrkB kinase activity rapidly and specifically during the induction of cortical plasticity in vivo. Contrary to the model, TrkB kinase activity was not required for any of the effects of monocular deprivation. When the deprived eye was re-opened during the critical period, cortical responses to it recovered. This recovery was blocked by TrkB inhibition. These findings suggest a more conventional trophic role for TrkB signaling in the enhancement of responses or growth of new connections, rather than a role in competition.

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Figure 1: Inhibition of TrkBF616A in the cortex by 1NM-PP1.
Figure 2: Effects of TrkB kinase inhibition during the critical period on visual cortical functions.
Figure 3: TrkB inactivation does not affect plasticity induced by monocular deprivation.
Figure 4: TrkB inactivation blocks the recovery of cortical responses to the previously deprived eye.
Figure 5: Acute optical imaging and single-unit recording confirm the requirement of TrkB kinase activity for recovery.

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Acknowledgements

The TrkBF616A mice were provided by D. Ginty and with the permission of CGI and Princeton University. We thank members of the laboratory and P. McQuillen for discussions, J. Cang for help with analyses of optical imaging data, A. Shreiber, C.M. Beal and T. Tran for technical assistance, Regeneron Pharmaceuticals for TrkB-IgG, and L. Reichardt for TrkB antibody. This study was supported by grants from the US National Institutes of Health (P50-MH077972, R37-EY02874, and T32-EY07120).

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Authors and Affiliations

  1. W.M. Keck Foundation Center for Integrative Neuroscience and Department of Physiology, 513 Parnassus Avenue, Room HSE-801, Box 0444, University of California San Francisco, San Francisco, 94143-0444, California, USA

    Megumi Kaneko, Jessica L Hanover & Michael P Stryker

  2. Departments of Cellular and Molecular Pharmacology, Genentech Hall, Room N-512B, Box 2280, 600 16th Street, University of California San Francisco, San Francisco, 94158-2517, California, USA

    Pamela M England

  3. Department of Pharmaceutical Chemistry, Genentech Hall, Room N-512B, Box 2280, 600 16th Street, University of California San Francisco, San Francisco, 94158-2517, California, USA

    Pamela M England

Authors
  1. Megumi Kaneko
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  2. Jessica L Hanover
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  4. Michael P Stryker
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Contributions

M.K. carried out all of the biochemical analysis, optical imaging and single-unit recordings using TrkBF616A and their appropriate control mice, prepared all of the figures (except for Supplementary Fig. 3) and wrote the first draft of the manuscript. J.L.H. carried out experiments on K252a and TrkB-IgG mice. P.M.E. supplied mutant mice and 1NM-PP1. M.K., P.M.E. and M.P.S. designed the experiments and assisted with data analysis and revision of the manuscript.

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Correspondence to Michael P Stryker.

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Kaneko, M., Hanover, J., England, P. et al. TrkB kinase is required for recovery, but not loss, of cortical responses following monocular deprivation. Nat Neurosci 11, 497–504 (2008). https://doi.org/10.1038/nn2068

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