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. 2020 Mar 17;14:56.
doi: 10.3389/fncel.2020.00056. eCollection 2020.

Experience-Dependent Changes in Myelin Basic Protein Expression in Adult Visual and Somatosensory Cortex

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Free PMC article

Experience-Dependent Changes in Myelin Basic Protein Expression in Adult Visual and Somatosensory Cortex

Kathryn M Murphy et al. Front Cell Neurosci. .
Free PMC article

Abstract

An experience-driven increase in oligodendrocytes and myelin in the somatosensory cortex (S1) has emerged as a new marker of adult cortical plasticity. That finding contrasts with the view that myelin is a structural brake on plasticity, and that contributes to ending the critical period (CP) in the visual cortex (V1). Despite the evidence that myelin-derived signaling acts to end CP in V1, there is no information about myelin changes during adult plasticity in V1. To address this, we quantified the effect of three manipulations that drive adult plasticity (monocular deprivation (MD), fluoxetine treatment or the combination of MD and fluoxetine) on the expression of myelin basic protein (MBP) in adult rat V1. In tandem, we validated that environmental enrichment (EE) increased cortical myelin by measuring MBP in adult S1. For comparison with the MBP measurements, three plasticity markers were also quantified, the spine markers drebrin E and drebrin A, and a plasticity maintenance marker Ube3A. First, we confirmed that EE increased MBP in S1. Next, that expression of the plasticity markers was affected in S1 by EE and in V1 by the visual manipulations. Finally, we found that after adult MD, MBP increased in the non-deprived V1 hemisphere, but it decreased in the deprived hemisphere, and those changes were not influenced by fluoxetine. Together, the findings suggest that modulation of myelin expression in adult V1 may reflect the levels of visually driven activity rather than synaptic plasticity caused by adult plasticity.

Keywords: adult plasticity; environmental enrichment (EE); monocular deprivation; myelin; myelin basic protein (MBP); somatosensory cortex; visual cortex (V1).

Figures

Figure 1
Figure 1
Illustration of the visual pathway to the deprived and non-deprived V1 hemispheres (A) and the tissue sampling regions (B). (A) The visual pathway is illustrated using gray lines to represent the deprived eye pathway and green lines the non-deprived eye pathway. About 90% of the rat visual pathway projection projects to the contralateral hemisphere so V1 opposite the MDed eye is the deprived hemisphere while the other V1 (ipsilateral) is non-deprived because it still receives strong input from the open eye (green). (B) The cortical regions sampled (S1 and V1) are illustrated in one hemisphere and in this study the samples were taken from different animals.
Figure 2
Figure 2
Expression of drebrin-E and drebrin-A in S1 and the deprived V1. (A,B) Drebrin E and drebrin A expression in S1 of control animals (n = 12), short-term environmental enrichment (S-EE; n = 6) and long-term EE (L-EE; n = 5). (A) In S1, expression of the immature drebrin E was reduced after L-EE (−41%, SEM 6.2%, p < 0.001). (B) In contrast, the mature drebrin A was increased after L-EE (+76%, SEM 36%, p < 0.01). (C,D) Drebrin E and drebrin A expression in V1 of animals reared with normal binocular vision (n = 6), 1-month fluoxetine (P70–98, n = 6), 1 week monocular deprivation (MD; P91–98, n = 8) or 1-month fluoxetine (P70–98) plus 1 week MD (P91–98, n = 8). In V1, both drebrin E and drebrin A were reduced after fluoxetine alone (FLX: drebrin-E: −32%, SEM 6.0%, p < 0.001; drebrin-A: −32%, SEM 3.2%, p < 0.001) or when fluoxetine was combined with MD (FLX MD: drebrin-E: −28%, SEM 7.4%, p < 0.001; drebrin-A: −17%, SEM 4.4%, p < 0.05). (E,F) An index of the relative expression of drebrin A and drebrin E was calculated where values <0 indicate more drebrin E and values >0 more drebrin A. (E) In V1, none of the treatment groups shifted the drebrin balance compared with normal. (F) In S1, both S-EE and L-EE shifted the drebrin balance to more drebrin A (S-EE p < 0.05, L-EE p < 0.01). *p < 0.05, **p < 0.01, ***p < 0.001.
Figure 3
Figure 3
Expression of myelin basic protein (MBP) and Ube3A in S1 and V1. (A) S-EE increased MBP expression (+56%, SEM 30%, p < 0.05) and (B) L-EE increased Ube3A (+18%, SEM 13%, p < 0.05). (C) MBP expression was increased in the non-deprived (ipsilateral) hemisphere after both MD (light gray; MD ipsi, +72%, SEM 32%, p < 0.05) and fluoxetine plus MD (pink; flx MD ipsi, +62%, SEM 18%, p < 0.01). There was a loss of MBP expression in the deprived (contralateral) hemisphere after both MD (dark gray; MD con, −27%, SEM 13%, p < 0.05) and fluoxetine plus MD (red; flx MD con, −17%, SEM 4.8%, p < 0.01). (D) There was a loss of Ube3A expression after MD (MD con, −45%, SEM 9.9%, p < 0.001) but an increase after MD plus fluoxetine (flx MD con, +56%, SEM 33%, p < 0.01). *p < 0.05, **p < 0.01, ***p < 0.001.
Figure 4
Figure 4
Hierarchical cluster analysis of adult V1. The high dimensional pattern of protein expression changes in V1 for the deprived (contralateral) and non-deprived (ipsilateral) hemispheres were analyzed by combining the measurements of MBP and Ube3A from this study with data for GluA2, PSD95, Gephyrin, Synapsin, and Synaptophysin from our previous study (Beshara et al., 2015). Correlation matrices are plotted to show the strength and direction (blue: negative; red: positive) of the pairwise Pearson’s R correlations between proteins for each condition and hemisphere. The inset with each panel shows the color-code and distribution of R values. The order of proteins was determined using unsupervised hierarchical clustering such that proteins with stronger correlations were nearby in the matrix: (A) normal, (B) fluoxetine, (C) MD contralateral (deprived) hemisphere, (D) fluoxetine and MD contralateral (deprived) hemisphere, (E) MD ipsilateral (non-deprived) hemisphere, and (F) fluoxetine and MD ipsilateral (non-deprived) hemisphere.

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References

    1. Akbik F. V., Bhagat S. M., Patel P. R., Cafferty W. B. J., Strittmatter S. M. (2013). Anatomical plasticity of adult brain is titrated by Nogo Receptor 1. Neuron 77, 859–866. 10.1016/j.neuron.2012.12.027 - DOI - PMC - PubMed
    1. Akbik F., Cafferty W. B. J., Strittmatter S. M. (2012). Myelin associated inhibitors: a link between injury-induced and experience-dependent plasticity. Exp. Neurol. 235, 43–52. 10.1016/j.expneurol.2011.06.006 - DOI - PMC - PubMed
    1. Ampuero E., Rubio F. J., Falcon R., Sandoval M., Diaz-Veliz G., Gonzalez R. E., et al. . (2010). Chronic fluoxetine treatment induces structural plasticity and selective changes in glutamate receptor subunits in the rat cerebral cortex. Neuroscience 169, 98–108. 10.1016/j.neuroscience.2010.04.035 - DOI - PubMed
    1. Balsor J. L., Murphy K. M. (2018). “Protocol for a high-throughput semiautomated preparation for filtered synaptoneurosomes,” in Synaptosomes Neuromethods, ed. Murphy K., editor. (New York, NY: Humana Press; ), 57–73.
    1. Barak B., Zhang Z., Liu Y., Nir A., Trangle S. S., Ennis M., et al. . (2019). Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioral and myelin alterations rescuable by a remyelinating drug. Nat. Neurosci. 22, 700–708. 10.1038/s41593-019-0380-9 - DOI - PubMed
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