Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons.

Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons.
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DOI:
10.1186/1756-6606-5-33
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发表时间:
2012-09-24
期刊:
影响因子:
3.6
通讯作者:
Whitsel BL
Whitsel BL
中科院分区:
医学3区
文献类型:
--
作者:
Lee J;Woo J;Favorov OV;Tommerdahl M;Lee CJ;Whitsel BL

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GABA是中枢神经系统中主要的抑制性神经递质,在成熟的大脑中也能产生兴奋。然而,尚未观察到皮层神经元中GABA兴奋的活动依赖形式。在这里,我们报告,在一个强烈的电刺激后,成年皮层神经元表现出短暂的GABA兴奋,持续约30秒。进行全细胞贴片记录,以评估短暂应用GABA对成年啮齿动物感觉运动皮质切片中锥体神经元的影响,在对第6层和下层白色物质之间的交界处进行1 s、20 Hz阈上电刺激(L 6/WM刺激)之前和之后。在L 6/WM刺激后,立即在柱状区域的中心产生神经元去极化的GABA喷。然而,无论是刺激前或刺激后30秒的GABA喷产生超极化的神经元。2-在用携带氯离子传感器Clomeleon的腺病毒感染的神经元中的光子成像显示,GABA诱导的去极化是由于刺激后[Cl-]i的增加。为了揭示GABA兴奋作用的空间范围,在刺激后立即应用GABAA受体激动剂异谷瓦辛,同时监测锥体神经元中的细胞内Ca 2+浓度。异古瓦辛引起锥体神经元[Ca 2 +]i的增加,特别是在柱的中心,但不是在柱的周边区域。Ca 2+信号的总体模式显示出沿刺激部位沿着的柱状分布。这些结果表明,众所周知的抑制性递质GABA迅速开关从超极化去极化突触活动在成年体感皮层神经元。
GABA, the major inhibitory neurotransmitter in CNS, has been demonstrated to paradoxically produce excitation even in mature brain. However activity-dependent form of GABA excitation in cortical neurons has not been observed. Here we report that after an intense electrical stimulation adult cortical neurons displayed a transient GABA excitation that lasted for about 30s. Whole-cell patch recordings were performed to evaluate the effects of briefly applied GABA on pyramidal neurons in adult rodent sensorimotor cortical slice before and after 1 s, 20 Hz suprathreshold electrical stimulation of the junction between layer 6 and the underlying white matter (L6/WM stimulation). Immediately after L6/WM stimulation, GABA puffs produced neuronal depolarization in the center of the column-shaped region. However, both prior to or 30s after stimulation GABA puffs produced hyperpolarization of neurons. 2-photon imaging in neurons infected with adenovirus carrying a chloride sensor Clomeleon revealed that GABA induced depolarization is due to an increase in [Cl-]i after stimulation. To reveal the spatial extent of excitatory action of GABA, isoguvacine, a GABAA receptors agonist, was applied right after stimulation while monitoring the intracellular Ca2+ concentration in pyramidal neurons. Isoguvacine induced an increase in [Ca2+]i in pyramidal neurons especially in the center of the column but not in the peripheral regions of the column. The global pattern of the Ca2+ signal showed a column-shaped distribution along the stimulation site. These results demonstrate that the well-known inhibitory transmitter GABA rapidly switches from hyperpolarization to depolarization upon synaptic activity in adult somatosensory cortical neurons.
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