GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo
GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo
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DOI：
10.1038/ncomms8750
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发表时间：
2015-07-01
影响因子：
16.6
通讯作者：
Holthoff, Knut
中科院分区：
文献类型：
--
作者：
Kirmse, Knut;Kummer, Michael;Holthoff, Knut
大量来自体外研究的证据表明，GABA在出生后早期发育过程中是去极化的。然而，GABA在完整发育的大脑中的作用模式尚不清楚。在这里，我们使用电生理学和钙离子成像技术相结合的方法来研究GABA对上皮质板细胞的体内效应。我们报道，在出生后(P)3-4天，GABA使麻醉小鼠枕叶皮质中的大多数未成熟神经元去极化。同时，GABA不能有效地激活电压门控钙通道，也不能诱发动作电位放电。阻断GABA(A)受体可抑制自发的网络活动，而变构激活GABA(A)受体则具有相反的作用。综上所述，我们的数据提供了证据，证明在体内，GABA作为一种去极化的神经递质，对新生儿(P3-4)新皮质的网络活动施加了抑制控制。
A large body of evidence from in vitro studies suggests that GABA is depolarizing during early postnatal development. However, the mode of GABA action in the intact developing brain is unknown. Here we examine the in vivo effects of GABA in cells of the upper cortical plate using a combination of electrophysiological and Ca2+-imaging techniques. We report that at postnatal days (P) 3-4, GABA depolarizes the majority of immature neurons in the occipital cortex of anaesthetized mice. At the same time, GABA does not efficiently activate voltage-gated Ca2+ channels and fails to induce action potential firing. Blocking GABA(A) receptors disinhibits spontaneous network activity, whereas allosteric activation of GABA(A) receptors has the opposite effect. In summary, our data provide evidence that in vivo GABA acts as a depolarizing neurotransmitter imposing an inhibitory control on network activity in the neonatal (P3-4) neocortex.