Orexin-A excites pyramidal neurons in layer 2/3 of the rat prefrontal cortex
Orexin-A excites pyramidal neurons in layer 2/3 of the rat prefrontal cortex
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DOI：
10.1016/j.neulet.2012.05.038
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发表时间：
2012-06
影响因子：
2.5
通讯作者：
Jie Yan;Chao He;J. Xia;Dan Zhang;Zhian Hu
中科院分区：
文献类型：
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作者：
Jie Yan;Chao He;J. Xia;Dan Zhang;Zhian Hu
食欲素是一种唤醒肽，在调节前额叶皮层（PFC）功能中起着重要作用。虽然食欲素已被证明可以增加内侧前额叶皮层（mPFC）深层神经元的兴奋性，但对它们对皮层内主要处理层2/3层的影响知之甚少。在这项研究中，我们研究了orexin-A的影响，锥体神经元在第2/3层的mPFC使用全细胞记录在大鼠脑片。我们观察到orexin-A通过突触后作用可逆地使2/3层锥体神经元去极化。这种去极化是浓度依赖性的，并通过食欲素受体1介导。在电压钳记录，orexin-A-诱导的电流减少更换内部K+与Cs+，去除外部Na+，或应用氟灭酸（非选择性阳离子通道的抑制剂）。Na~+/Ca~（2+）交换体阻断剂SN-6不影响orexin-A的兴奋作用。此外，当外加溶液中含有低浓度Na+时，orexin-A诱导的电流在Ek附近发生逆转。当在正常的外部溶液中用含Cs+的移液管记录时，电流的反向电位约为− 25 mV。这些数据表明K+通道和非选择性阳离子通道参与食欲素-A的作用。orexin-A对mPFC 2/3层神经元的直接兴奋作用可能参与了对PFC活动的调节，并在认知唤醒中发挥作用。
The arousal peptides, orexins, play an important role in regulating the function of the prefrontal cortex (PFC). Although orexins have been shown to increase the excitability of deep-layer neurons in the medial prefrontal cortex (mPFC), little is known about their effect on layer 2/3, the main intracortical processing layer. In this study, we investigated the effect of orexin-A on pyramidal neurons in layer 2/3 of the mPFC using whole-cell recordings in rat brain slices. We observed that orexin-A reversibly depolarized layer 2/3 pyramidal neurons through a postsynaptic action. This depolarization was concentration-dependent and mediated via orexin receptor 1. In voltage-clamp recordings, the orexin-A-induced current was reduced by the replacement of internal K+with Cs+, removal of external Na+, or an application of flufenamic acid (an inhibitor of nonselective cation channels). A blocker of Na+/Ca2+exchangers (SN-6) did not influence the excitatory effect of orexin-A. Moreover, the current induced by orexin-A reversed nearEkwhen the external solution contained low levels of Na+. When recording with Cs+-containing pipettes in normal external solution, the reversal potential of the current was approximately −25 mV. These data suggest an involvement of both K+channels and nonselective cation channels in the effect of orexin-A. The direct excitatory action of orexin-A on layer 2/3 mPFC neurons may contribute to the modulation of PFC activity, and play a role in cognitive arousal.