Working memory deficits in retinoid X receptor γ-deficient mice
Working memory deficits in retinoid X receptor γ-deficient mice
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DOI：
10.1101/lm.89805
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发表时间：
2005-05-01
影响因子：
2
通讯作者：
Krezel, W
中科院分区：
文献类型：
--
作者：
Wietrzych, M;Meziane, H;Krezel, W
最近研究表明，类维生素A信号传导是啮齿动物记忆功能所需的。为了剖析这一要求所涉及的行为和分子机制，我们分析了携带维甲酸受体RAR β和RXR γ无效突变的小鼠的空间和识别工作记忆。在Y-迷宫中的自发交替和在T-迷宫中的延迟位置不匹配（DNMTP）测试中，双突变体出现空间工作记忆缺陷。然而，这些突变小鼠获得，空间位置参考或右/左歧视任务的T-迷宫设置，表明基本的感觉运动功能，空间定向，和动机因素是不可能占赤字在工作记忆敏感的任务。双突变小鼠也缺乏新的物体识别在中间，但不是短的延迟。RXR γ似乎是调节工作记忆的功能性主要受体，因为RXR γ而不是RAR β单无效突变小鼠表现出与双突变体中观察到的缺陷相似的缺陷。这种调制的机制可能与额叶和嗅周皮质中RXR γ的功能有关，在这些结构中，我们检测到RXR γ表达，并且在功能上涉及工作记忆过程。
Retinoid signaling has been recently shown to be required for mnemonic functions in rodents. To dissect the behavioral and molecular mechanisms involved in this requirement, we have analyzed the spatial and recognition working memory in mice carrying null mutations of retinoid receptors RAR beta and RXR gamma. Double mutants appeared deficient in spatial working memory as tested in spontaneous alternation in the Y-maze and delayed nonmatch to place (DNMTP) test in the T-maze. These mutant mice did acquire, however, spatial place reference or right/left discrimination tasks in the T-maze set-up, indicating that basic sensorimotor functions, spatial orientation, and motivational factors are unlikely to account for deficits in working memory-sensitive tasks. Double-mutant mice were also deficient in novel object recognition at intermediate, but not short delays. RXR gamma appeared to be the functionally predominant receptor in modulation of the working memory, as RXR gamma, but not RAR beta single null mutant mice exhibited deficits similar to those observed in the double mutants. The mechanism of this modulation is potentially related to functions of RXR gamma in frontal and perirhinal cortex, structures in which we detected RXR gamma expression and which are functionally implicated in working memory processes.