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出生时眼球摘除会促进大鼠初级体感皮层中桶状结构的扩张,而不是增加经验依赖性神经元活动的水平,这种扩张是由于发育时间的改变所致。

Shifts in developmental timing, and not increased levels of experience-dependent neuronal activity, promote barrel expansion in the primary somatosensory cortex of rats enucleated at birth.

机构信息

Departmento de Biología Celular y Fisiología, Programa de Posgrado en Ciencias Bilógicas, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, Distrito Federal, México.

出版信息

PLoS One. 2013;8(1):e54940. doi: 10.1371/journal.pone.0054940. Epub 2013 Jan 25.

Abstract

Birth-enucleated rodents display enlarged representations of whiskers (i.e., barrels of the posteromedial subfield) in the primary somatosensory cortex. Although the historical view maintains that barrel expansion is due to incremental increases in neuronal activity along the trigeminal pathway during postnatal development, recent evidence obtained in experimental models of intramodal plasticity challenges this view. Here, we re-evaluate the role of experience-dependent neuronal activity on barrel expansion in birth-enucleated rats by combining various anatomical methods and sensory deprivation paradigms. We show that barrels in birth-enucleated rats were already enlarged by the end of the first week of life and had levels of metabolic activity comparable to those in control rats at different ages. Dewhiskering after the postnatal period of barrel formation did not prevent barrel expansion in adult, birth-enucleated rats. Further, dark rearing and enucleation after barrel formation did not lead to expanded barrels in adult brains. Because incremental increases of somatosensory experience did not promote barrel expansion in birth-enucleated rats, we explored whether shifts of the developmental timing could better explain barrel expansion during the first week of life. Accordingly, birth-enucleated rats show earlier formation of barrels, accelerated growth of somatosensory thalamocortical afferents, and an earlier H4 deacetylation. Interestingly, when H4 deacetylation was prevented with a histone deacetylases inhibitor (valproic acid), barrel specification timing returned to normal and barrel expansion did not occur. Thus, we provide evidence supporting that shifts in developmental timing modulated through epigenetic mechanisms, and not increased levels of experience dependent neuronal activity, promote barrel expansion in the primary somatosensory cortex of rats enucleated at birth.

摘要

出生时被去核的啮齿动物在初级体感皮层中显示出更大的胡须(即后内侧亚区的桶状结构)代表区。尽管历史观点认为,桶状结构的扩大是由于出生后发育过程中三叉神经通路中神经元活动的增量增加,但最近在感觉模态内可塑性的实验模型中获得的证据挑战了这一观点。在这里,我们通过结合各种解剖学方法和感觉剥夺范式,重新评估经验依赖性神经元活动对出生时去核大鼠桶状结构扩大的作用。我们表明,出生时去核大鼠的桶状结构在出生后的第一周已经扩大,并且其代谢活性水平与不同年龄的对照组大鼠相当。在桶状结构形成后的出生后时期去胡须并不能防止成年出生时去核大鼠的桶状结构扩大。此外,暗饲养和桶状结构形成后的去核也不会导致成年大脑中的桶状结构扩大。由于感觉经验的增量增加并没有促进出生时去核大鼠的桶状结构扩大,我们探索了发育时间的转变是否可以更好地解释出生后第一周的桶状结构扩大。因此,出生时去核的大鼠表现出更早的桶状结构形成、体感丘脑皮质传入纤维的加速生长以及更早的 H4 去乙酰化。有趣的是,当用组蛋白去乙酰化酶抑制剂(丙戊酸)阻止 H4 去乙酰化时,桶状结构的形成时间恢复正常,并且桶状结构不会扩大。因此,我们提供的证据支持发育时间的转变通过表观遗传机制调节,而不是增加经验依赖性神经元活动的水平,促进了出生时去核大鼠初级体感皮层的桶状结构扩大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba40/3556040/389c590a11ed/pone.0054940.g001.jpg

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