NR2C in the thalamic reticular nucleus; effects of the NR2C knockout.

NR2C in the thalamic reticular nucleus; effects of the NR2C knockout.
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DOI:
10.1371/journal.pone.0041908
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Lisman JE
Lisman JE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang Y;Buonanno A;Vertes RP;Hoover WB;Lisman JE

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NMDAR拮抗剂可以在丘脑网状核(nRT)中诱发δ频率爆发。确定了这种振荡的机制;拮抗剂阻断NR 2C样电导,其在静息电位下具有低Mg阻断,因此可以响应于环境谷氨酸而贡献静息内向电流。阻止该电流会使细胞超极化,使T型Ca通道失活,从而触发Delta频率爆发。假设NR 2C样电导的基础是:(1)NR 2C的转录本在丘脑中丰富,(2)突触诱发的NMDAR电流的电流-电压曲线具有NR 2C的低整流特性。在目前的研究中,我们试图确定产生NMDAR电流的通道是NR 2C样的还是实际上由含有NR 2C的受体组成。我们研究了NR 2C基因敲除小鼠nRT突触诱发NMDAR电流的电流-电压曲线。在野生型小鼠中,电流是弱电压依赖性的,如先前在大鼠中观察到的。这种弱整流在NR 2C KO小鼠中不存在。相反,NR 2C KO对前额叶皮质锥体细胞中的强整流NMDAR电流没有影响。这些结果表明,通常在nRT中观察到的低整流是由于NR 2C。
NMDAR antagonists can evoke delta frequency bursting in the nucleus reticularis of the thalamus (nRT). The mechanism of this oscillation was determined; antagonist blocks an NR2C-like conductance that has low Mg block at resting potential and thus can contribute a resting inward current in response to ambient glutamate. Block of this current hyperpolarizes the cell, deinactivating T-type Ca channels and thus triggering delta frequency bursting. The basis for assuming a NR2C-like conductance was that (1) transcripts for NR2C are abundant in the thalamus and (2) the current-voltage curve of the synaptically evoked NMDAR current has the low rectification characteristic of NR2C. In the current study, we have sought to determine whether the channels that generate the NMDAR current are NR2C-like or are actually comprised of receptors containing NR2C. We studied the current-voltage curve of synaptically evoked NMDAR current in the nRT of NR2C knockout mice. In wild-type mice, the current was weakly voltage dependent, as previously observed in rats. This weak rectification was absent in NR2C KO mice. In contrast, NR2C KO had no effect on the strongly rectifying NMDAR current in pyramidal cells of the prefrontal cortex. These results demonstrate that the low rectification normally observed in the nRT is due to NR2C.
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