Rietman M Liset, Sommeijer J-P, Levelt Christiaan N, Heimel J Alexander
Department of Molecular Visual Plasticity, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences Amsterdam, Netherlands.
Front Neurosci. 2012 Feb 1;6:11. doi: 10.3389/fnins.2012.00011. eCollection 2012.
Many studies have been devoted to the identification of genes involved in experience-dependent plasticity in the visual cortex. To discover new candidate genes, we have reexamined data from one such study on ocular dominance (OD) plasticity in recombinant inbred BXD mouse strains. We have correlated the level of plasticity with the gene expression data in the neocortex that have become available for these same strains. We propose that genes with a high correlation are likely to play a role in OD plasticity. We have tested this hypothesis for genes whose inactivation is known to affect OD plasticity. The expression levels of these genes indeed correlated with OD plasticity if their levels showed strong differences between the BXD strains. To narrow down our candidate list of correlated genes, we have selected only those genes that were previously found to be regulated by visual experience and associated with pathways implicated in OD plasticity. This resulted in a list of 32 candidate genes. The list contained unproven, but not unexpected candidates such as the genes for IGF-1, NCAM1, NOGO-A, the gamma2 subunit of the GABA(A) receptor, acetylcholine esterase, and the catalytic subunit of cAMP-dependent protein kinase A. This demonstrates the viability of our approach. More interestingly, the following novel candidate genes were identified: Akap7, Akt1, Camk2d, Cckbr, Cd44, Crim1, Ctdsp2, Dnajc5, Gnai1, Itpka, Mapk8, Nbea, Nfatc3, Nlk, Npy5r, Phf21a, Phip, Ppm1l, Ppp1r1b, Rbbp4, Slc1a3, Slit2, Socs2, Spock3, St8sia1, Zfp207. Whether all these novel candidates indeed function in OD plasticity remains to be established, but possible roles of some of them are discussed in the article.
许多研究致力于鉴定参与视觉皮层经验依赖性可塑性的基因。为了发现新的候选基因,我们重新审视了一项关于重组近交BXD小鼠品系眼优势(OD)可塑性的此类研究数据。我们将可塑性水平与这些相同品系新皮层中已有的基因表达数据进行了关联。我们提出,具有高相关性的基因可能在OD可塑性中发挥作用。我们已经针对那些已知其失活会影响OD可塑性的基因检验了这一假设。如果这些基因在BXD品系之间的水平显示出强烈差异,那么它们的表达水平确实与OD可塑性相关。为了缩小我们的相关基因候选列表,我们只选择了那些先前被发现受视觉经验调节并与OD可塑性相关途径有关的基因。这产生了一份包含32个候选基因的列表。该列表包含未经证实但并非出乎意料的候选基因,如胰岛素样生长因子1(IGF-1)、神经细胞黏附分子1(NCAM1)、轴突生长抑制因子A(NOGO-A)、γ-氨基丁酸A(GABA(A))受体的γ2亚基、乙酰胆碱酯酶以及环磷酸腺苷(cAMP)依赖性蛋白激酶A的催化亚基等基因。这证明了我们方法的可行性。更有趣的是,鉴定出了以下新的候选基因:Akap7、Akt1、Camk2d、Cckbr、Cd44、Crim1、Ctdsp2、Dnajc5、Gnai1、Itpka、Mapk8、Nbea、Nfatc3、Nlk、Npy5r、Phf21a、Phip、Ppm1l、Ppp1r1b、Rbbp4、Slc1a3、Slit2、Socs2、Spock3、St8sia1、Zfp207。所有这些新候选基因是否确实在OD可塑性中发挥作用仍有待确定,但本文讨论了其中一些基因可能的作用。