α2-Noradrenergic receptors activation enhances excitability and synaptic integration in rat prefrontal cortex pyramidal neurons via inhibition of HCN currents
α2-Noradrenergic receptors activation enhances excitability and synaptic integration in rat prefrontal cortex pyramidal neurons via inhibition of HCN currents
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DOI：
10.1113/jphysiol.2007.141671
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发表时间：
2007-10-15
影响因子：
5.5
通讯作者：
Lavin, A.
中科院分区：
文献类型：
--
作者：
Carr, David B.;Andrews, Glenn D.;Lavin, A.
刺激PFC内的α 2-去甲肾上腺素能（NA）受体可改善工作记忆表现。这种改善是伴随着选择性增加PFC神经元的活动在延迟期间，虽然负责这种增强反应的细胞机制在很大程度上是未知的。在这里，我们使用电流和电压钳记录来表征第V-VI层PFC锥体神经元对α 2-NA受体刺激的反应-α 2-NA受体激活产生静息膜电位的小超极化，这伴随着输入电阻和诱发放电的增加。电压钳分析表明，α 2-NA受体刺激抑制铯和ZD 7288敏感的超极化激活（HCN）内向电流。α 2-NA刺激对HCN电流的抑制不依赖于腺苷酸环化酶，而是需要激活PLC-PKC连接的信号通路。与直接阻断HCN通道类似，α 2-NA受体刺激在远端诱发的EPSP序列中产生了时间总和的显著增强。α 2-NA受体刺激的这些双重效应-膜超极化和增强的时间整合-一起产生PFC锥体神经元对兴奋性突触输入的响应的总体增益的增加。净效应是抑制孤立的兴奋性输入，同时增强对突触活动的连贯爆发的反应。
Stimulation Of alpha 2-noradrenergic (NA) receptors within the PFC improves working memory performance. This improvement is accompanied by a selective increase in the activity of PFC neurons during delay periods, although the cellular mechanisms responsible for this enhanced response are largely unknown. Here we used current and voltage clamp recordings to characterize the response of layer V-VI PFC pyramidal neurons to alpha 2-NA receptor stimulation- alpha 2-NA receptor activation produced a small hyperpolarization of the resting membrane potential, which was accompanied by an increase in input resistance and evoked firing. Voltage clamp analysis demonstrated that alpha 2-NA receptor stimulation inhibited a caesium and ZD7288-sensitive hyperpolarization-activated (HCN) inward current. Suppression of HCN current by alpha 2-NA stimulation was not dependent on adenylate cyclase but instead required activation of a PLC-PKC linked signalling pathway. Similar to direct blockade of HCN channels, alpha 2-NA receptor stimulation produced a significant enhancement in temporal summation during trains of distally evoked EPSPs. These dual effects Of a2-NA receptor stimulation - membrane hyperpolarization and enhanced temporal integration - together produce an increase in the overall gain of the response of PFC pyramidal neurons to excitatory synaptic input. The net effect is the suppression of isolated excitatory inputs while enhancing the response to a coherent burst of synaptic activity.