Department of Physiology, Anhui Medical College, Anhui 230601, China.
Department of Histology and Embryology, School of Basic Medical Sciences, Anhui Medical University, Anhui 230032, China.
Neurosci Lett. 2019 Sep 14;709:134374. doi: 10.1016/j.neulet.2019.134374. Epub 2019 Jul 13.
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.
感觉皮层的拓扑图由投射到皮层不同区域的丘脑皮质传入纤维(TCAs)组成。感觉皮层拓扑图的形成是新皮层功能成熟的前提。研究表明,躯体感觉皮层拓扑图的形成和丘脑皮质突触的成熟依赖于环磷酸腺苷(cAMP)-蛋白激酶 A(PKA)信号通路。AKAP5 是一种支架蛋白(在人类中也称为 AKAP79 或在啮齿动物中称为 AKAP150;AKAP79/150),作为一种信号枢纽,将 cAMP 和 PKA 信号联系起来。AKAP5 是否在躯体感觉皮层发育过程中参与拓扑图的形成和丘脑皮质突触的成熟尚不清楚。在这里,我们生成了皮层特异性 AKAP5 敲除小鼠(CxAKAP5KO),以研究其在躯体感觉皮层发育中的作用。我们发现 CxAKAP5KO 小鼠表现出皮质桶状图受损。电生理记录显示,在出生后发育过程中,CxAKAP5KO 小鼠的丘脑皮质突触中 AMPA/NMDA 比值降低,沉默突触增加。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 对于躯体感觉皮层中拓扑图的形成和丘脑皮质突触的成熟以及皮质神经元的形态发育都是必需的。