The Depolarizing Action of GABA Controls Early Network Activity in the Developing Hippocampus
The Depolarizing Action of GABA Controls Early Network Activity in the Developing Hippocampus
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DOI：
10.1007/s12035-010-8147-z
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发表时间：
2011-04-01
影响因子：
5.1
通讯作者：
Lagostena, Laura
中科院分区：
文献类型：
--
作者：
Cherubini, Enrico;Griguoli, Marilena;Lagostena, Laura
在出生后的早期，γ-氨基丁酸（GABA），在成年人中的主要抑制性递质，兴奋靶向神经元的氯离子的外向流量，这是由于阳离子-氯离子共转运蛋白NKCC 1和KCC 2之间的不平衡，分别参与氯化物的摄取和挤出。这种效应有助于在发育中的海马体中产生同步的网络活动或巨大的去极化电位（GDPs）。在这里，我们回顾了一些最近的数据有关的机制，GDPs的产生和他们的功能作用，提高在发育不良的GABA能和神经元突触的突触功效。在成年期，由于氯稳态的变化和GABA从超极化到去极化的转变而重塑神经元回路，与包括癫痫在内的几种神经系统疾病有关。最近提供的证据表明，在慢性神经生长因子剥夺小鼠表达的渐进性年龄依赖性神经退行性病变类似于阿尔茨海默病患者中观察到的，减少表达的mRNA编码的Kcc 2基因和GABA的去极化作用导致神经元海马网络的重组。这可能代表了一种新的机制，通过这种机制，GABA能信号转导抵消了神经退行性疾病中突触活性的丧失。
Early in postnatal life gamma-aminobutyric acid (GABA), the primary inhibitory transmitter in adults, excites targeted neurons by an outwardly directed flux of chloride which results from the unbalance between the cation-chloride cotransporters NKCC1 and KCC2, involved in chloride uptake and extrusion, respectively. This effect contributes to generate synchronized network activity or giant depolarizing potentials (GDPs) in the developing hippocampus. Here, we review some recent data concerning the mechanisms by which GDPs are generated and their functional role in enhancing synaptic efficacy at poorly developed GABAergic and glutamatergic synapses. In adulthood, reshaping neuronal circuits due to changes in chloride homeostasis and to the shift of GABA from hyperpolarizing to depolarizing, has been implicated in several neurological disorders, including epilepsy. Evidence has been recently provided that in chronically nerve growth factor-deprived mice expressing a progressive age-dependent neurodegenerative pathology resembling that observed in patients with Alzheimer's disease, the reduced expression of mRNA encoding for the Kcc2 gene and the depolarizing action of GABA lead to the reorganization of the neuronal hippocampal network. This may represent a novel mechanism by which GABAergic signaling counterbalances the loss of synaptic activity in neurodegenerative diseases.