Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo
Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo
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DOI：
10.1523/jneurosci.5169-06.2007
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发表时间：
2007-05-09
影响因子：
5.3
通讯作者：
Poo, Mu-ming
中科院分区：
文献类型：
--
作者：
Cancedda, Laura;Fiumelli, Hubert;Poo, Mu-ming
GABA对胚胎和新生儿皮层神经元产生兴奋作用，但这种GABA兴奋的体内功能基本上是未知的。使用在子宫内电穿孔，我们消除了兴奋作用的GABA在一个亚群的大鼠心室祖细胞和皮质神经元来自这些祖细胞的过早表达的Cl-转运蛋白KCC 2，证实了GABA诱导的电流和GABAA受体阻断后的静息膜电位的逆转电位的变化。我们发现，径向迁移到层II/III的体感皮层的神经元来自转染的祖细胞没有受到显着影响，但其形态成熟显着受损。此外，通过过度表达内向整流K+通道（其降低静息膜电位）来降低体内皮质神经元的神经元兴奋性，模仿了过早KCC 2表达的效果。因此，早期GABA兴奋引起的膜去极化是体内新生皮层神经元形态成熟的关键。
GABA exerts excitatory actions on embryonic and neonatal cortical neurons, but the in vivo function of this GABA excitation is essentially unknown. Using in utero electroporation, we eliminated the excitatory action of GABA in a subpopulation of rat ventricular progenitors and cortical neurons derived from these progenitors by premature expression of the Cl- transporter KCC2, as confirmed by the changes in the reversal potential of GABA-induced currents and the resting membrane potential after GABAA receptor blockade. We found that radial migration to layer II/III of the somatosensory cortex of neurons derived from the transfected progenitors was not significantly affected, but their morphological maturation was markedly impaired. Furthermore, reducing neuronal excitability of cortical neurons in vivo by overexpressing an inward-rectifying K+ channel, which lowered the resting membrane potential, mimicked the effect of premature KCC2 expression. Thus, membrane depolarization caused by early GABA excitation is critical for morphological maturation of neonatal cortical neurons in vivo.