Neuroscience Division, Pablo de Olavide University, Seville, Spain.
PLoS One. 2010 Aug 12;5(8):e12123. doi: 10.1371/journal.pone.0012123.
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.
在表达伪狂犬病病毒即刻早期蛋白 IE180(TgIE96)的转基因小鼠的小脑显著缩小,其组织架构严重紊乱,导致严重的共济失调。因此,TgIE96 小鼠可被用作研究小脑回路在不同学习任务中参与的实验模型。对 3 个月大的 TgIE96 小鼠在各种行为测试中的表现进行了研究,包括联想学习(经典眨眼条件反射)、物体识别、空间定位(水迷宫)、惊跳反应和前脉冲抑制以及被动回避,并与野生型小鼠进行了比较。野生型和 TgIE96 小鼠表现出相似的反射性诱发眨眼反应,并以相似的学习曲线获得了经典条件反射的眨眼反应,无论是痕迹还是延迟条件反射范式。两组小鼠在物体识别测试中也表现出相似的性能。然而,在本研究中包含的其他三个测试中,它们表现出了显著的差异。尽管两组动物都能够游泳,但 TgIE96 小鼠在允许的时间内未能学习水迷宫任务。强烈声音引起的惊跳反应在对照组和 TgIE96 小鼠中相似,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存在明显缺陷。这些结果表明,小脑对于经典眨眼条件反射和物体识别任务的表现不是必需的,但似乎对于水迷宫、前脉冲抑制和被动回避测试的正确表现是必要的。