Distribution of language-related Cntnap2 protein in neural circuits critical for vocal learning.

Distribution of language-related Cntnap2 protein in neural circuits critical for vocal learning.
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DOI:
10.1002/cne.23394
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发表时间:
2014-01-01
影响因子:
2.5
通讯作者:
White, Stephanie A.
White, Stephanie A.
中科院分区:
医学3区
文献类型:
--
作者:
Condro, Michael C.;White, Stephanie A.

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接触蛋白相关蛋白样2 (Cntnap2)基因的变异是语言相关障碍的危险因素,包括自闭症谱系障碍、特异性语言障碍和口吃。鸣禽是研究人类语言障碍的有用模型,因为它们有共同的声乐学习能力,这依赖于相似的皮质-基底神经节回路和遗传因素。在这里,我们研究了Cntnap2蛋白在斑胸草雀大脑中的表达,斑胸草雀是一种鸣禽,雄性而不是雌性学习它们的求偶歌曲。我们假设Cntnap2在声乐学习物种中具有重叠的功能,并期望在斑胸草雀大脑中与歌唱相关的区域找到蛋白质表达。我们进一步预计,由于这两种分子物种的亚细胞定位不同,这种膜结合蛋白的分布可能不完全反映其mRNA的分布。我们发现Cntnap2蛋白在几个与周围组织相关的歌曲控制区域中富集,特别是在成年男性中,而不是在女性中,arcopallium (RA)的健壮核中,这是一个类似于人类第5层初级运动皮层的皮质歌曲控制区域。这种两性二态表达的开始与发育中的男性感觉运动学习的开始一致。雄性RA的富集是由于核内的投射神经元的表达,以及从侧毛大细胞核向RA的皮质投射的神经末梢的额外表达。Cntnap2蛋白在斑胸草雀大脑中的表达支持了这种分子影响神经连接的假设,这种神经连接对不同分类类别的声乐学习至关重要。
Variants of the contactin associated protein-like 2 (Cntnap2) gene are risk factors for language-related disorders including autism spectrum disorder, specific language impairment, and stuttering. Songbirds are useful models for study of human speech disorders due to their shared capacity for vocal learning, which relies on similar cortico-basal ganglia circuitry and genetic factors. Here, we investigate Cntnap2 protein expression in the brain of the zebra finch, a songbird species in which males, but not females, learn their courtship songs. We hypothesize that Cntnap2 has overlapping functions in vocal learning species, and expect to find protein expression in song-related areas of the zebra finch brain. We further expect that the distribution of this membrane-bound protein may not completely mirror its mRNA distribution due to the distinct subcellular localization of the two molecular species. We find that Cntnap2 protein is enriched in several song control regions relative to surrounding tissues, particularly within the adult male, but not female, robust nucleus of the arcopallium (RA), a cortical song control region analogous to human layer 5 primary motor cortex. The onset of this sexually dimorphic expression coincides with the onset of sensorimotor learning in developing males. Enrichment in male RA appears due to expression in projection neurons within the nucleus, as well as to additional expression in nerve terminals of cortical projections to RA from the lateral magnocellular nucleus of the nidopallium. Cntnap2 protein expression in zebra finch brain supports the hypothesis that this molecule affects neural connectivity critical for vocal learning across taxonomic classes.
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发表时间: 2013-03-19
影响因子: 11.1
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