Serial Reversal Learning in an Olfactory Discrimination Task in 3xTg-AD Mice

Male and female 3xTg-AD mice and their B6129F2/J wildtype controls, between 5 and 24 months of age, were tested on a series of 18 olfactory discrimination and reversal tasks in an operant olfactometer. All mice learned the odour discriminations and reversals to a criterion of 85% correct, but the 3xTg-AD mice made fewer errors than the B6129F2/J mice in the odour discriminations and in the first six reversal learning tasks. Many mice showed evidence of near errorless learning and on the reversal tasks, the 3xTg-AD mice showed more instances of near errorless learning than the B6129F2/J mice. There was no evidence of an age effect on odour discrimination, but there was a decrease in errorless reversal learning in aged B6129F2/J mice. In long-term memory tests there was an increase in number of errors made, but no genotype difference. The high level of performance indicates that the mice were able to develop a learning-to-learn strategy. The finding that the 3xTg-AD mice out-performed their littermate controls provides an example of paradoxical functional facilitation in these mice.

选取5至24月龄的雄性与雌性3xTg-AD小鼠（3xTg-AD mice）及其同窝B6129F2/J野生型对照小鼠（B6129F2/J wildtype controls），在操作式嗅觉仪（operant olfactometer）中开展共计18项嗅觉辨别（olfactory discrimination）与反转学习任务（reversal learning tasks）的行为测试。所有受试小鼠均达到85%正确率的任务标准以完成嗅觉辨别与反转学习流程，但在嗅觉辨别阶段与前6项反转学习任务中，3xTg-AD小鼠的错误次数显著少于B6129F2/J野生型小鼠。大量受试小鼠展现出近乎零错误学习（near errorless learning）的行为特征，且在反转学习任务中，3xTg-AD小鼠出现近乎零错误学习的案例数量多于B6129F2/J野生型小鼠。嗅觉辨别阶段未观察到年龄效应，但老年B6129F2/J野生型小鼠的零错误反转学习能力出现显著下降。在长期记忆测试（long-term memory tests）中，受试小鼠的错误次数均有所增加，但未发现基因型相关的性能差异。较高的任务完成水平表明，受试小鼠能够形成学习如何学习（learning-to-learn）策略。3xTg-AD小鼠的表现优于同窝野生型对照这一实验发现，为这类小鼠的反常功能易化（paradoxical functional facilitation）现象提供了典型实例。