Facilitation of long-term potentiation and memory in mice lacking nociception receptors
Facilitation of long-term potentiation and memory in mice lacking nociception receptors
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DOI：
10.1038/29073
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发表时间：
1998-08-06
期刊：
影响因子：
64.8
通讯作者：
Takeshima, H
中科院分区：
文献类型：
--
作者：
Manabe, T;Noda, Y;Takeshima, H
肽伤害感受素（也称为Nociceptin FQ）在大脑中起作用，产生各种药理学作用，包括痛觉过敏和运动功能减退（1，2）。痛敏素受体使用鸟嘌呤核苷酸结合蛋白介导腺苷酸环化酶的抑制、钾通道的激活和钙通道的抑制（3）。使用敲除小鼠已经表明，伤害感受素受体不是调节伤害性反应或运动活性所必需的，但调节听觉功能（4）。在这里，我们表明，缺乏孤啡肽受体的小鼠比对照小鼠具有更强的学习能力和更好的记忆。组织学分析揭示了在海马中的伤害感受素前体和伤害感受素受体的表达，被认为参与学习和记忆的方面。此外，受体缺陷小鼠表现出更大的长时程增强在海马CAI区比对照组小鼠，没有明显的变化，突触前或突触后电生理特性。这些结果表明，伤害感受素受体的损失的结果在获得的功能突变的记忆过程和长时程增强机制在CA 1，可能是由于改变细胞内信号转导系统的神经元。
The peptide nociceptin (also named orphanin FQ) acts in the brain to produce various pharmacological effects, including hyperalgesia and hypolocomotion(1,2). The nociceptin receptor uses guanine-nucleotide-binding proteins to mediate the inhibition of adenylyl cyclase, the activation of potassium channels and inhibition of calcium channels(3). It has been shown using knockout mice that the nociceptin receptor is not required for regulation of nociceptive responses or locomotion activity, but modulates the auditory function(4). Here we show that mice lacking the nociceptin receptor possess greater learning ability and have better memory than control mice. Histological analysis revealed the expression of both the nociceptin precursor and the nociceptin receptor in the hippocampus, thought to take part in aspects of learning and memory. Moreover, the receptor-deficient mice showed larger long-term potentiation in the hippocampal CAI region than control mice, without apparent changes in presynaptic or postsynaptic electrophysiological properties. These results show that the loss of the nociceptin receptor results in a gain-of-function mutation in both the memory process and the long-term potentiation mechanism in CA1, perhaps as a result of altered intracellular signal transduction systems in neurons.