Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors
Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors
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DOI：
10.1016/j.neures.2006.10.020
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发表时间：
2007-02-01
影响因子：
2.9
通讯作者：
Yanai, Kazuhiko
中科院分区：
文献类型：
--
作者：
Dai, Hongmei;Kaneko, Kenya;Yanai, Kazuhiko
先前的药理学实验提供了相互矛盾的发现，描述了神经元组胺对学习和记忆的促进和抑制作用。在这里，我们检查了编码组胺 HI 或 H2 受体基因无效突变的小鼠的学习和记忆以及突触可塑性，以阐明这些受体在学习和记忆过程中的作用。学习和记忆通过多种行为任务进行评估，包括物体识别、巴恩斯迷宫和恐惧调节。这些行为任务高度依赖于前额皮质、海马体或杏仁核的功能。与相应的野生型 (WT) 小鼠相比，HI 受体基因敲除 (H1KO) 和 H2 受体基因敲除 (H2KO) 小鼠的物体识别和巴恩斯迷宫表现均显着受损。相反，H1KO 和 H2KO 小鼠均表现出比各自的 WT 小鼠更好的听觉和情境冻结获取能力。此外，我们还检测了 H1KO 和 H2KO 小鼠及其各自的 WT 小鼠海马 CA1 区的长时程增强 (LTP)。与各自的 WT 小鼠相比，H I KO 和 H2KO 小鼠海马 CA1 区的 LTP 显着降低。总之，我们的结果表明，H1 和 H2 受体都参与额叶皮层、杏仁核和海马相互作用的学习和记忆过程。 (c) 2006 Elsevier Ireland Ltd 和日本神经科学学会。版权所有。
Previous pharmacological experiments provide conflicting findings that describe both facilitatory and inhibitory effects of neuronal histamine on learning and memory. Here, we examined learning and memory and synaptic plasticity in mice with a null mutation of gene coding histamine HI or H2 receptor in order to clarify the role of these receptors in learning and memory processes. Learning and memory were evaluated by several behavioral tasks including object recognition, Barnes maze and fear conditioning. These behavioral tasks are highly dependent on the function of prefrontal cortex, hippocampus or amygdala. Object recognition and Barnes maze performance were significantly impaired in both HI receptor gene knockout (H1KO) and H2 receptor gene knockout (H2KO) mice when compared to the respective wild-type (WT) mice. Conversely, both H1KO and H2KO mice showed better auditory and contextual freezing acquisition than their respective WT mice. Furthermore, we also examined long-term potentiation (LTP) in the CA1 area of hippocampus in H1KO and H2KO mice and their respective WT mice. LTP in the CA1 area of hippocampus was significantly reduced in both H I KO and H2KO mice when compared with their respective WT mice. In conclusion, our results demonstrate that both H1 and H2 receptors are involved in learning and memory processes for which the frontal cortex, amygdala and hippocampus interact. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.