The A-current modulates learning via NMDA receptors containing the NR2B subunit.

The A-current modulates learning via NMDA receptors containing the NR2B subunit.
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DOI:
10.1371/journal.pone.0024915
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Carrión AM
Carrión AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fontán-Lozano Á;Suárez-Pereira I;González-Forero D;Carrión AM

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突触可塑性涉及短期和长期事件,尽管这些过程背后的分子机制尚未完全了解。瞬态 A 型 K+ 电流 (IA) 通过调节动作电位的反向传播和塑造突触输入来控制 CA1 锥体神经元树突的兴奋性。在这里,我们研究了 IA 的减少如何影响认知过程和突触可塑性。使用用 IA 抑制剂 4-AP 处理的野生型小鼠和缺乏 DREAM 蛋白(IA 的转录抑制因子和调节剂)的小鼠,我们证明 IA 的损伤会降低学习的刺激阈值和早期 LTP 的诱导。两个模型中的海马电记录都揭示了基础电振荡特性向低θ频率的变化。此外,我们证明,IA 减少诱导的学习促进需要激活包含 NR2B 亚基的 NMDA 受体。总之,这些发现表明 IA 和含有 NR2B 的 NMDA 受体在学习调节中的活性之间存在平衡。
Synaptic plasticity involves short- and long-term events, although the molecular mechanisms that underlie these processes are not fully understood. The transient A-type K+ current (IA) controls the excitability of the dendrites from CA1 pyramidal neurons by regulating the back-propagation of action potentials and shaping synaptic input. Here, we have studied how decreases in IA affect cognitive processes and synaptic plasticity. Using wild-type mice treated with 4-AP, an IA inhibitor, and mice lacking the DREAM protein, a transcriptional repressor and modulator of the IA, we demonstrate that impairment of IA decreases the stimulation threshold for learning and the induction of early-LTP. Hippocampal electrical recordings in both models revealed alterations in basal electrical oscillatory properties toward low-theta frequencies. In addition, we demonstrated that the facilitated learning induced by decreased IA requires the activation of NMDA receptors containing the NR2B subunit. Together, these findings point to a balance between the IA and the activity of NR2B-containing NMDA receptors in the regulation of learning.
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