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, 309 (5744), 2222-6

Experience-driven Plasticity of Visual Cortex Limited by Myelin and Nogo Receptor

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Experience-driven Plasticity of Visual Cortex Limited by Myelin and Nogo Receptor

Aaron W McGee et al. Science.

Abstract

Monocular deprivation normally alters ocular dominance in the visual cortex only during a postnatal critical period (20 to 32 days postnatal in mice). We find that mutations in the Nogo-66 receptor (NgR) affect cessation of ocular dominance plasticity. In NgR-/- mice, plasticity during the critical period is normal, but it continues abnormally such that ocular dominance at 45 or 120 days postnatal is subject to the same plasticity as at juvenile ages. Thus, physiological NgR signaling from myelin-derived Nogo, MAG, and OMgp consolidates the neural circuitry established during experience-dependent plasticity. After pathological trauma, similar NgR signaling limits functional recovery and axonal regeneration.

Figures

Fig. 1
Fig. 1
Expression of myelin, NgR, and CSPG in mouse visual cortex during the critical period for OD plasticity. (A) P40 visual cortex labeled for parvalbumin (green in merge) and wisteria floribunda agglutinin (red in merge). (B) Sections as in (A), labeled for parvalbumin (red in merge) and NgR (green in merge). (C) Homogenates of visual cortex were immunoblotted with the indicated antibodies. Microdensitometry revealed that the concentration of any one protein varied by <20% across these ages, and there were no significant changes in protein levels with age. (D) P20 to P60 visual cortex labeled with antibodies to MBP. Layers I to VI are indicated (right). (E) Distribution of relative MBP intensity within visual cortex. (F) A higher magnification image of MBP distribution at P60. Error bars reflect SEM; n = 3 mice. Asterisks denote significant differences (P < 0.05) between P20 and P26 versus P40 and P60 for both genotypes. Scale bars in [(A) and (B)] = 100 μm, in (D) = 200 μm, and in (F) = 100 μm.
Fig. 2
Fig. 2
NgR and Nogo-A/B mutant mice are sensitive to monocular deprivation after the critical period. (A) OD histogram and average WOD score for NgR mutant mice receiving monocular deprivation (black ellipse beneath the abscissa) at P24. (B to G) OD histograms and WOD scores as in (A), for wild-type (WT), NgR, and Nogo-A/B mutant mice with and without monocular deprivation. (H) Mean WOD scores for monocularly deprived and nondeprived animals across genotype and age. Bars represent the WOD values in [(A) to (G)]; error bars are SEM. Double asterisks denote significant differences (P < 0.001) of P45 and P120 WOD scores from P45 WT nondeprived and monocularly deprived scores.
Fig. 3
Fig. 3
GAD65 and tPA are normal in NgR mutant mice. (A) Homogenates of visual cortex from wild-type (WT) and NgR mice were immunoblotted with antibodies to GAD65. (B) Densitometry of GAD65 immunoreactivity from blots of P60 visual cortex from WT and NgR mutants (n = 4 mice). (C) P60 visual cortex of WT and NgR−/− mice labeled with antibodies to GAD65. (D) Microdensitometric level of GAD65 immunoreactivity in the neuropil of visual cortex from WT and NgR mutants. (E) Density of parvalbumin-immunopositive interneurons in visual cortex of WT and NgR mice, per 0.5 mm2. (F) Immunoblot as in (A), with an antibody to tPA. (G) Quantification of tPA expression as in (B). (H) Confocal images of WT P60 visual cortex double-labeled with antibodies to MBP and to parvalbumin. White arrows point to immunopositive fibers in the αMBP and αParv panels, one that colocalizes in the merged image (right arrow) and others that do not (left and upper arrows). A higher magnification image, outlined by the white rectangle, is shown on the far right. Scale bar for [(C) and (H)] = 20 μm; for the higher magnification image, scale bar = 10 μm.

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