Motor-Coordination-Dependent Learning, More than Others, Is Impaired in Transgenic Mice Expressing Pseudorabies Virus Immediate-Early Protein IE180

Motor-Coordination-Dependent Learning, More than Others, Is Impaired in Transgenic Mice Expressing Pseudorabies Virus Immediate-Early Protein IE180
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DOI:
10.1371/journal.pone.0012123
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发表时间:
2010-08-12
期刊:
影响因子:
3.7
通讯作者:
Delgado-Garcia, Jose M.
Delgado-Garcia, Jose M.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lopez-Ramos, Juan C.;Tomioka, Yukiko;Delgado-Garcia, Jose M.

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表达伪狂犬病病毒立即早期蛋白IE180(TgIE96)的转基因小鼠小脑的大小大幅减少,其组织结构严重紊乱,导致严重的共济失调。因此,TgIE96小鼠可用作研究小脑回路参与不同学习任务的实验模型。在各种行为测试中研究了三个月大的TgIE96小鼠的表现,包括联想学习(经典眨眼条件反射)、物体识别、空间定向(水迷宫)、惊吓反应和前脉冲抑制以及被动回避,并与野生型小鼠进行比较。野生型和TgIE96小鼠呈现出相似的反射性诱发眨眼,并获得了经典的条件性眼睑反应,对于跟踪和延迟条件化范例具有相似的学习曲线。两组小鼠在物体识别测试中也有相似的表现。然而,他们在本研究中包括的其他三项测试中显示出显着差异。虽然两组动物都能游泳,但TgIE96小鼠在允许的时间内未能学习水迷宫任务。在对照组和TgIE96小鼠中,对严重音调的惊吓反应相似,但后者无法产生显著的前脉冲抑制。TgIE96小鼠在正确完成被动回避测试方面也表现出明显的缺陷。这些结果表明,小脑不是必不可少的经典眨眼条件反射的性能和物体识别任务,但似乎是必要的水迷宫,前脉冲抑制,和被动回避测试的适当性能。
The cerebellum in transgenic mice expressing pseudorabies virus immediate-early protein IE180 (TgIE96) was substantially diminished in size, and its histoarchitecture was severely disorganized, resulting in severe ataxia. TgIE96 mice can therefore be used as an experimental model to study the involvement of cerebellar circuits in different learning tasks. The performance of three-month-old TgIE96 mice was studied in various behavioral tests, including associative learning (classical eyeblink conditioning), object recognition, spatial orientation (water maze), startle response and prepulse inhibition, and passive avoidance, and compared with that of wild-type mice. Wild-type and TgIE96 mice presented similar reflexively evoked eyeblinks, and acquired classical conditioned eyelid responses with similar learning curves for both trace and delay conditioning paradigms. The two groups of mice also had similar performances during the object recognition test. However, they showed significant differences for the other three tests included in this study. Although both groups of animals were capable of swimming, TgIE96 mice failed to learn the water maze task during the allowed time. The startle response to a severe tone was similar in both control and TgIE96 mice, but the latter were unable to produce a significant prepulse inhibition. TgIE96 mice also presented evident deficits for the proper accomplishment of a passive avoidance test. These results suggest that the cerebellum is not indispensable for the performance of classical eyeblink conditioning and for object recognition tasks, but seems to be necessary for the proper performance of water maze, prepulse inhibition, and passive avoidance tests.