Abstract
Numerous protein kinases have been implicated in visual cortex plasticity, but the role of serine/threonine protein phosphatases has not yet been established. Calcineurin, the only known Ca2+/calmodulin-activated protein phosphatase in the brain, has been identified as a molecular constraint on synaptic plasticity in the hippocampus and on memory. Using transgenic mice overexpressing calcineurin inducibly in forebrain neurons, we now provide evidence that calcineurin is also involved in ocular dominance plasticity. A transient increase in calcineurin activity is found to prevent the shift of responsiveness in the visual cortex following monocular deprivation, and this effect is reversible. These results imply that the balance between protein kinases and phosphatases is critical for visual cortex plasticity.
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Acknowledgements
This work was supported by Public Health Service Grant R01 EY00053 and the Connecticut Lions Eye Research Foundation. I.M.M. is supported by the University of Zürich, the Swiss Federal Institute of Technology, the Swiss National Science Foundation, Swiss National Centre for Competence in Research 'Neural Plasticity and Repair', European Molecular Biology Organization, Human Frontier Science Program. N.W.D. is a Senior Science Investigator of Research to Prevent Blindness. We thank D. Winder for providing the mice, A. LaRue for help with PCR, R. Munton for help with synaptosomal preparations, and Y. Rao for help with the LTD measurements.
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Supplementary Fig. 1
Lack of ocular dominance plasticity with an intact onset of the critical period in CNO mice. (a) Calcineurin transgene is suppressed by doxycycline treatment from birth to P21 after the typical onset of the critical period (P19, Gordon and Stryker, 1996). The animals are monocularly deprived at P28, and recordings are performed four days later. (b) Columns showing ocular dominance distribution after monocular deprivation in CNO mice, which is identical to that in non–deprived wild–type mice (solid line), but significantly different from that in deprived wild–type mice (dash line, P < 0.0001, χ 2 test), indicating the impaired ocular dominance plasticity. (GIF 5 kb)
Supplementary Fig. 2
LTD is normal in visual cortex in CNO mice. LTD was induced by 15-min 1-Hz presynaptic stimulation paired with postsynaptic depolarization in CNO mice (77 ± 5%, n = 8; P < 0.01, compare to the baseline), which was identical to that observed in wild type animals (74.7 ± 3.1%). (GIF 17 kb)
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Yang, Y., Fischer, Q., Zhang, Y. et al. Reversible blockade of experience-dependent plasticity by calcineurin in mouse visual cortex. Nat Neurosci 8, 791–796 (2005). https://doi.org/10.1038/nn1464
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DOI: https://doi.org/10.1038/nn1464