Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception.

Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception.
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DOI:
10.1038/ncomms15488
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发表时间:
2017-05-23
影响因子:
16.6
通讯作者:
Pizzorusso T
Pizzorusso T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mazziotti R;Baroncelli L;Ceglia N;Chelini G;Sala GD;Magnan C;Napoli D;Putignano E;Silingardi D;Tola J;Tognini P;Arthur JSC;Baldi P;Pizzorusso T

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已知microRNA(miRNAs)介导转录后基因调控,但其在出生后脑发育中的作用仍然很少被探索。我们发现在小鼠视皮层的功能成熟过程中,许多miRNAs的表达受到显著调节,其中miR-132/212家族是上调最多的miRNAs之一。miR-132/miR-212缺失小鼠中miR-132/miR-212下调的转录物显著富集在miR-132/miR-212推定靶点和上调的基因中。在功能水平上,miR-132/212缺失影响皮层神经元感受野的发育,确定定向偏好的双眼匹配的特定损伤,但保持定向和方向选择性不变。这种缺陷与视觉悬崖测试中的深度知觉降低有关。前脑兴奋性神经元中miR-132/212的缺失复制了双眼匹配缺陷。因此,miR-132/212家族在特定发育窗口期间形成视皮层的年龄依赖性转录组,导致双眼皮层细胞的成熟和深度感知。miR-132/212与关键期的眼优势可塑性有关。在这里,作者表明miR-132/212调节参与视觉皮层成熟的基因的表达,并且缺乏miR-132/212的小鼠在方向偏好的双眼匹配中表现出缺陷,这导致深度感知受损。
MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception. miR-132/212 has been implicated in ocular dominance plasticity during the critical period. Here the authors show that miR-132/212 regulates the expression of genes involved in visual cortex maturation, and that mice lack miR-132/212 show deficits in binocular matching of orientation preferences, which leads to impaired depth perception.