Song Seoho, Mitchell Donald E, Crowder Nathan A, Duffy Kevin R
Department of Psychology and Neuroscience, Dalhousie University, Life Sciences Centre, Halifax, Nova Scotia, Canada, B3H 4R2.
J Comp Neurol. 2015 Oct 1;523(14):2111-26. doi: 10.1002/cne.23781. Epub 2015 May 12.
A principal characteristic of the mammalian visual system is its high capacity for plasticity in early postnatal development during a time commonly referred to as the critical period. The progressive diminution of plasticity with age is linked to the emergence of a collection of molecules called molecular brakes that reduce plasticity and stabilize neural circuits modified by earlier visual experiences. Manipulation of braking molecules either pharmacologically or though experiential alteration enhances plasticity and promotes recovery from visual impairment. The stability of neural circuitry is increased by intermediate filamentous proteins of the cytoskeleton such as neurofilaments and α-internexin. We examined levels of these intermediate filaments within cat and human primary visual cortex (V1) across development to determine whether they accumulate following a time course consistent with a molecular brake. In both species, levels of intermediate filaments increased considerably throughout early postnatal life beginning shortly after the peak of the critical period, with the highest levels measured in adults. Neurofilament phosphorylation was also observed to increase throughout development, raising the possibility that posttranslational modification by phosphorylation reduces plasticity due to increased protein stability. Finally, an approach to scale developmental time points between species is presented that compares the developmental profiles of intermediate filaments between cats and humans. Although causality between intermediate filaments and plasticity was not directly tested in this study, their accumulation relative to the critical period indicates that they may contribute to the decline in plasticity with age, and may also constrain the success of treatments for visual disorders applied in adulthood.
哺乳动物视觉系统的一个主要特征是其在出生后早期发育阶段具有高度可塑性，这一时期通常被称为关键期。随着年龄增长，可塑性逐渐降低，这与一类被称为分子制动器的分子的出现有关，这些分子会降低可塑性并稳定因早期视觉经验而改变的神经回路。通过药理学手段或改变经验来操纵制动分子，可增强可塑性并促进视觉损伤后的恢复。细胞骨架的中间丝蛋白，如神经丝和α-中间丝蛋白，可增加神经回路的稳定性。我们研究了猫和人类初级视觉皮层（V1）在整个发育过程中这些中间丝的水平，以确定它们是否按照与分子制动器一致的时间进程积累。在这两个物种中，中间丝的水平在出生后早期显著增加，始于关键期高峰期后不久，在成年时达到最高水平。在整个发育过程中还观察到神经丝磷酸化增加，这增加了一种可能性，即磷酸化的翻译后修饰由于蛋白质稳定性增加而降低了可塑性。最后，提出了一种在不同物种间缩放发育时间点的方法，该方法比较了猫和人类之间中间丝的发育情况。尽管本研究未直接测试中间丝与可塑性之间的因果关系，但它们相对于关键期的积累表明，它们可能导致可塑性随年龄下降，并且可能还会限制成年期应用的视觉障碍治疗的成功率。
