Conditioned response suppression in the IntelliCage: assessment of mouse strain differences and effects of hippocampal and striatal lesions on acquisition and retention of memory
Conditioned response suppression in the IntelliCage: assessment of mouse strain differences and effects of hippocampal and striatal lesions on acquisition and retention of memory
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DOI：
10.1016/j.bbr.2010.05.019
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发表时间：
2010-12
影响因子：
2.7
通讯作者：
V. Võikar;G. Colacicco;O. Gruber;Elisabetta Vannoni;H. Lipp;D. Wolfer
中科院分区：
文献类型：
--
作者：
V. Võikar;G. Colacicco;O. Gruber;Elisabetta Vannoni;H. Lipp;D. Wolfer
IntelliCage允许在不处理小鼠的情况下，在家庭笼环境中对各种行为进行全自动连续测试。在这里，我们测试了在IntelliCage之外度过一段时间延迟后是否保留了条件性回避。在训练过程中，在四个学习角之一的鼻子戳惩罚与空气喷。训练24小时后，将小鼠置于常规笼中24小时。在该间隔的最后18小时期间，小鼠被剥夺水，然后返回到IntelliCage进行探测试验，其中允许在所有角落饮水。C57 BL/6小鼠在训练期间在惩罚角落中产生了显著的鼻子戳抑制，并且将回避进行到下面的探测试验。重复实验，在分配给单个小鼠的不同角落进行惩罚，揭示了类似的表现模式。在探针试验中，不同品系之间的比较显示，与C57 BL/6小鼠相比，DBA/2和B6 D2 F1小鼠的鼻塞抑制减少，尽管在短（1-s）空气抽吸训练期间的错误率相似。然而，当空气抽吸延长至角落访问结束时，探针试验中三种菌株的性能相等。6天后鼻戳抑制显著消退。训练和探测试验之间的延长间隔（7天）导致DBA/2小鼠的抑制丧失，但在C57 BL/6和B6 D2 F1小鼠中没有。额外的实验表明，在探测试验的性能是依赖于一组复杂的intramaze线索。对双侧海马或背外侧纹状体兴奋性毒性损伤的小鼠进行的测试显示，学习这项任务依赖于完整的海马，而不是完整的纹状体。总之，这里提出的条件性鼻塞抑制试验对遗传差异和海马病变都很敏感。该试验可用于筛选海马功能受损的突变小鼠，比标准记忆试验更有效。
The IntelliCage allows fully automated continuous testing of various behaviours in the home cage environment without handling the mice. Here we tested whether conditioned avoidance is retained after a time period delay spent outside the IntelliCage. During the training, nosepokes in one of the four learning corners were punished with an air-puff. After 24h of training, the mice were placed in regular cages for 24h. During the last 18h of this interval, the mice were water deprived and then returned to the IntelliCage for a probe trial where drinking was allowed in all corners. The C57BL/6 mice developed a significant suppression of nosepoking in the punished corner during training, and the avoidance was carried over to the following probe trial. Repetition of the experiment by delivering punishment in a different corner assigned to individual mice revealed a similar performance pattern. Comparison between the different strains revealed a reduced nosepoke suppression in DBA/2 and B6D2F1 mice as compared to C57BL/6 mice in the probe trial, despite similar error rates during the training with short (1-s) air-puffs. However, the performance of the three strains in the probe trial were equalised when the air-puffs were prolonged until the end of the corner visit. Significant extinction of the nosepoke suppression occurred after 6 days. A prolonged interval (7 days) between the training and the probe trial resulted in a loss of suppression in DBA/2 mice, but not in C57BL/6 and B6D2F1 mice. Additional experiments revealed that performance in the probe trial was dependent on a complex set of intramaze cues. Testing of mice with bilateral excitotoxic lesions of the hippocampus or dorso-lateral striatum revealed that learning this task was dependent on an intact hippocampus, but not on an intact striatum. In summary, the conditioned nosepoke suppression test presented here is sensitive to both genetic differences and hippocampal lesions. This test could be applied to the screening of mutant mice with impaired hippocampal functions more efficiently than those of the standard memory tests.