Maturation of thalamocortical synapses in the somatosensory cortex depends on neocortical AKAP5 expression

Maturation of thalamocortical synapses in the somatosensory cortex depends on neocortical AKAP5 expression
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体感皮层丘脑皮层突触的成熟取决于新皮层 AKAP5 的表达

DOI:
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发表时间:
2019-09
影响因子:
2.5
通讯作者:
Hong Li
Hong Li
中科院分区:
医学4区
文献类型:
--
作者:
Min Zhang;Meifang Lu;Hao Huang;Xiaoyan Liu;Haoran Su;Hong Li

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感觉皮层地形图由丘脑皮质传入(TCA)的有序阵列组成,这些传入投射到皮质的不同区域。感觉皮层地形图的形成是新皮质功能成熟的先决条件。研究表明,体感皮层地形图的形成和丘脑皮质突触的成熟依赖于环腺苷5‘-单磷酸(CAMP)-蛋白激酶A(PKA)信号通路。AKAP5是一种骨架蛋白(在人类中也称为AKAP79,在啮齿动物中称为AKAP150;AKAP79/150),作为连接cAMP和PKA信号的信号枢纽。AKAP5是否在地形图的形成和丘脑皮质突触的成熟中发挥作用尚不清楚。在这里,我们产生了皮层特异的AKAP5-.基因敲除小鼠(CxAKAP5KO)来检查它在体感皮质发育中的作用。我们发现.CxAKAP5KO小鼠显示受损的皮质桶状图。电生理记录显示,CxAKAP5KO小鼠在出生后发育过程中,丘脑皮质突触的AMPA/NMDA比值降低,沉默突触增多。对第四层皮质神经元的形态分析表明,这些神经元的树突细化异常。这些结果表明,AKAP5对丘脑皮质突触的地形图形成和成熟以及躯体感觉皮质神经元的形态发育都是必需的。
Sensory cortex topographic maps consist of organized arrays of thalamocortical afferents (TCAs) that project into.distinct areas of the cortex. Formation of topographic maps in sensory cortices is a prerequisite for functional.maturation of the neocortex. Studies have shown that the formation of topographic maps and the maturation of.thalamocortical synapses in the somatosensory cortex depend on the cyclic adenosine 5′-monophosphate-.(cAMP)-protein kinase A (PKA) signaling pathway. AKAP5 is a scaffold protein (also called AKAP79 in humans.or AKAP150 in rodents; AKAP79/150) that serves as a signaling hub that links cAMP and PKA signaling..Whether AKAP5 plays a role in topographic map formation and the maturation of thalamocortical synapses.during development of the somatosensory cortex is still unknown. Here, we generated cortex-specific AKAP5-.knockout mice (CxAKAP5KO) to examine its roles in somatosensory cortex development. We found that.CxAKAP5KO mice displayed impaired cortical barrel maps. Electrophysiological recordings showed that the.AMPA/NMDA ratio was reduced, and silent synapses were increased in thalamocortical synapses of CxAKAP5KO.mice during postnatal development. Morphological analysis of layer IV cortical neurons demonstrated that.dendritic refinement of these neurons was abnormal. These results indicate that AKAP5 is necessary for both.topographic map formation and maturation of thalamocortical synapses as well as morphological development.of cortical neurons in the somatosensory cortex.
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发表时间: 2007-05
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