Histamine induces KCNQ channel-dependent gamma oscillations in rat hippocampus via activation of the H1 receptor
Histamine induces KCNQ channel-dependent gamma oscillations in rat hippocampus via activation of the H1 receptor
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DOI：
10.1016/j.neuropharm.2017.03.003
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发表时间：
2017-05-15
影响因子：
4.7
通讯作者：
Fisahn, Andre
中科院分区：
文献类型：
--
作者：
Andersson, Richard;Galter, Dagmar;Fisahn, Andre
组胺是一种胺能神经递质，调节中枢神经系统的觉醒、唤醒和注意力。组胺受体一直是开发有利于认知的药物来治疗阿尔茨海默病和精神分裂症等疾病的目标。包括注意力在内的认知功能与伽马振荡密切相关，伽马振荡是一种在30-80赫兹范围内的有节奏的电活动模式，依赖于兴奋性锥体细胞和抑制性快速尖峰神经元的同步活动。我们开始探索组胺是否在河马校园中促进伽马振荡。用原位杂交方法证实了组胺受体亚型1、2和3在大鼠CA3区锥体层有表达。我们发现，在体外，锥体细胞和快速放电的中间神经元都能去极化并增加动作电位的放电，以响应组胺。组胺受体的激活在海马区的CA3区产生剂量依赖的瞬时伽马振荡-伽马节律生成器的位置。我们还证明了这种组胺效应是不依赖于毒碱受体的。使用特定的拮抗剂，我们提供了组胺伽玛心律失常发生具体依赖于H1受体的证据。组胺还使锥体细胞和快速放电的中间神经元去极化，并增加锥体细胞的膜电阻。由于KCNQ通道开放剂ICA110381的应用消除了这种振荡，膜电阻的增加潜在地通过抑制钾通道而介导。综上所述，我们的数据展示了在海马区产生伽马振荡的新的生理机制，并提示KCNQ通道在这种与认知相关的大脑活动中发挥作用。(C)2017爱思唯尔有限公司。保留所有权利。
Histamine is an aminergic neurotransmitter, which regulates wakefulness, arousal and attention in the central nervous system. Histamine receptors have been the target of efforts to develop pro-cognitive drugs to treat disorders such as Alzheimer's disease and schizophrenia. Cognitive functions including attention are closely associated with gamma oscillations, a rhythmical electrical activity pattern in the 30-80 Hz range, which depends on the synchronized activity of excitatory pyramidal cells and inhibitory fast-spiking interneurons.We set out to explore whether histamine has a role in promoting gamma oscillations in the hippo-campus. Using in-situ hybridization we demonstrate that histamine receptor subtypes 1, 2 and 3 are expressed in stratum pyramidale of area CA3 in rats. We show that both pyramidal cells and fast-spiking interneurons depolarize and increase action potential firing in response to histamine in vitro. The activation of histamine receptors generates dose-dependent, transient gamma oscillations in area CA3 of the hippocampus - the locus of the gamma rhythm generator. We also demonstrate that this histamine effect is independent of muscarinic receptors.Using specific antagonists we provide evidence that histamine gamma rhythmogenesis specifically depends on the H1 receptor. Histamine also depolarized both pyramidal cells and fast-spiking interneurons and increased membrane resistance in pyramidal cells. The increased membrane resistance is potentially mediated by the inhibition of potassium channels because application of the KCNQ channel opener ICA110381 abolished the oscillations.Taken together our data demonstrate a novel and physiological mechanism for generating gamma oscillations in hippocampus and suggest a role for KCNQ channels in this cognition-relevant brain activity. (C) 2017 Elsevier Ltd. All rights reserved.