KCC2 Regulates Dendritic Spine Formation in a Brain-Region Specific and BDNF Dependent Manner.
KCC2 Regulates Dendritic Spine Formation in a Brain-Region Specific and BDNF Dependent Manner.
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DOI：
10.1093/cercor/bhy198
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发表时间：
2018-11-01
期刊：
影响因子：
--
通讯作者：
Di Cristo G
中科院分区：
文献类型：
--
作者：
Awad PN;Amegandjin CA;Szczurkowska J;Carriço JN;Fernandes do Nascimento AS;Baho E;Chattopadhyaya B;Cancedda L;Carmant L;Di Cristo G
KCC2是神经元中主要的氯化物挤出器。KCC2表达的时空调节协调了发育向抑制性GABA能驱动的转变和突触的形成。KCC2在突触形成中的作用在不同的大脑区域是否相似尚不清楚。首先，我们发现，KCC2的亚细胞定位，但不是整体KCC2的表达水平，不同的皮质和海马在出生后的第一周。我们进行了位点特异性子宫内电穿孔的KCC2 cDNA的目标无论是海马CA1区或体感皮质锥体神经元。我们发现KCC2的过早表达显著降低了CA1神经元的棘密度，而在皮质神经元中则有相反的效果。这些效应是细胞自主的，因为海马和皮质器官型培养物中KCC2的单细胞生物射弹过表达也分别诱导树突棘密度的减少和增加。此外，我们发现其过早表达对棘密度的影响依赖于BDNF水平。最后，我们发现KCC2对树突棘的作用依赖于海马中的氯转运蛋白功能，而在皮层中观察到的作用相反。总之，这些结果表明，KCC2调节树突棘发育及其潜在机制是脑区域特异性的。
KCC2 is the major chloride extruder in neurons. The spatiotemporal regulation of KCC2 expression orchestrates the developmental shift towards inhibitory GABAergic drive and the formation of glutamatergic synapses. Whether KCC2’s role in synapse formation is similar in different brain regions is unknown. First, we found that KCC2 subcellular localization, but not overall KCC2 expression levels, differed between cortex and hippocampus during the first postnatal week. We performed site-specific in utero electroporation of KCC2 cDNA to target either hippocampal CA1 or somatosensory cortical pyramidal neurons. We found that a premature expression of KCC2 significantly decreased spine density in CA1 neurons, while it had the opposite effect in cortical neurons. These effects were cell autonomous, because single-cell biolistic overexpression of KCC2 in hippocampal and cortical organotypic cultures also induced a reduction and an increase of dendritic spine density, respectively. In addition, we found that the effects of its premature expression on spine density were dependent on BDNF levels. Finally, we showed that the effects of KCC2 on dendritic spine were dependent on its chloride transporter function in the hippocampus, contrary to what was observed in cortex. Altogether, these results demonstrate that KCC2 regulation of dendritic spine development, and its underlying mechanisms, are brain-region specific.
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