Moon J, Ota K T, Driscoll L L, Levitsky D A, Strupp B J
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
Dev Psychobiol. 2008 Jul;50(5):473-85. doi: 10.1002/dev.20308.
This study was designed to further assess cognitive and affective functioning in a mouse model of Fragile X syndrome (FXS), the Fmr1(tm1Cgr) or Fmr1 "knockout" (KO) mouse. Male KO mice and wild-type littermate controls were tested on learning set and reversal learning tasks. The KO mice were not impaired in associative learning, transfer of learning, or reversal learning, based on measures of learning rate. Analyses of videotapes of the reversal learning task revealed that both groups of mice exhibited higher levels of activity and wall-climbing during the initial sessions of the task than during the final sessions, a pattern also seen for trials following an error relative to those following a correct response. Notably, the increase in both behavioral measures seen early in the task was significantly more pronounced for the KO mice than for controls, as was the error-induced increase in activity level. This pattern of effects suggests that the KO mice reacted more strongly than controls to the reversal of contingencies and pronounced drop in reinforcement rate, and to errors in general. This pattern of effects is consistent with the heightened emotional reactivity frequently described for humans with FXS.
本研究旨在进一步评估脆性X综合征(FXS)小鼠模型Fmr1(tm1Cgr)或Fmr1“敲除”(KO)小鼠的认知和情感功能。雄性KO小鼠和野生型同窝对照小鼠接受了学习集和逆向学习任务测试。基于学习率的测量,KO小鼠在联想学习、学习迁移或逆向学习方面并未受损。对逆向学习任务录像带的分析显示,两组小鼠在任务初始阶段的活动水平和爬壁行为均高于最终阶段,相对于正确反应后的试验,错误反应后的试验也呈现出这种模式。值得注意的是,任务早期观察到的这两种行为指标的增加在KO小鼠中比对照组更为明显,错误引发的活动水平增加也是如此。这种效应模式表明,KO小鼠对意外情况的逆转、强化率的显著下降以及一般错误的反应比对照组更强烈。这种效应模式与经常描述的患有FXS的人类增强的情绪反应性一致。