Chen Hung-Lun, Chen Chien-Fu F, Huang Han-Bin
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Front Behav Neurosci. 2022 Feb 2;16:808978. doi: 10.3389/fnbeh.2022.808978. eCollection 2022.
C57BL/6 is the most widely used mouse strain in the laboratories. Two substrains of C57BL/6, C57BL/6J (B6J), and C57BL/6N (B6N) are well-known backgrounds for genetic modification and have been shown difference in quite a few tests, including open field test, rotarod test, and Morris water maze. However, difference between these two substrains in olfaction-dependent behaviors remains unknown. Here, we used olfactory two-alternative choice task, which is modified to have two training stages, to evaluate animals' ability in instrumental learning and olfactory association. In the first (rule learning) stage, the mice were trained to use the operant chamber to collect water rewards. An odor cue was provided in the procedure, with no indication about reward locations. In the following (discrimination learning) stage, two odor cues were provided, with each indicating a specific water port. The animals were rewarded upon correct port choices following cue deliveries. We found that during young adulthood (7-10 weeks old), proportionally more B6J than B6N mice were able to pass rule learning (58.3% vs. 29.2%) and ultimately acquire this task (54.2% vs. 25%), with the two substrains showing similar pass rates in discrimination learning (92.9% vs. 85.7%). Surprisingly, at a more mature age (17 weeks old), this substrain difference disappeared. Mature B6N mice had a significant improvement in pass percentages of rule learning and overall task, whereas similar improvement was not observed in the B6J counterparts. Instead, mature B6J mice had an improved speed in rule learning and overall task. We further examined behavioral patterns of 8-week-old B6J and B6N mice in the olfactory habituation or dishabituation test. We observed normal olfactory habituation from subjects of both substrains, with the B6J mice exhibiting stronger investigative responses to newly presented odorants. These results reveal for the first time that B6J and B6N mice are different in acquisition processes of a behavioral task that requires instrumental learning and olfactory association, and that maturation appears to employ different effects on these two substrains during these processes. Furthermore, young adult B6J and B6N mice might be similar in olfactory habituation but different in the olfactory aspects of novelty seeking.
C57BL/6是实验室中使用最广泛的小鼠品系。C57BL/6的两个亚系，C57BL/6J（B6J）和C57BL/6N（B6N）是基因改造的著名背景品系，并且在包括旷场试验、转棒试验和莫里斯水迷宫在内的不少测试中已显示出差异。然而，这两个亚系在嗅觉相关行为上的差异仍不清楚。在此，我们使用了经过修改以具有两个训练阶段的嗅觉二选一任务，来评估动物的工具性学习和嗅觉关联能力。在第一个（规则学习）阶段，训练小鼠使用操作箱来获取水奖励。在这个过程中提供一种气味线索，但没有关于奖励位置的提示。在接下来的（辨别学习）阶段，提供两种气味线索，每种线索指示一个特定的水口。动物在气味线索呈现后做出正确的水口选择时会得到奖励。我们发现，在成年早期（7 - 10周龄）时，能够通过规则学习的B6J小鼠比例比B6N小鼠更高（58.3%对29.2%），并且最终掌握这项任务的比例也更高（54.2%对25%），而这两个亚系在辨别学习中的通过率相似（92.9%对85.7%）。令人惊讶的是，在更成熟的年龄（17周龄）时，这种亚系差异消失了。成熟的B6N小鼠在规则学习和整体任务的通过率上有显著提高，而B6J小鼠则没有观察到类似的提高。相反，成熟的B6J小鼠在规则学习和整体任务中的速度有所提高。我们进一步在嗅觉习惯化或去习惯化测试中检查了8周龄B6J和B6N小鼠的行为模式。我们观察到两个亚系的小鼠都有正常的嗅觉习惯化，并且B6J小鼠对新呈现的气味剂表现出更强的探究反应。这些结果首次揭示，B6J和B6N小鼠在需要工具性学习和嗅觉关联的行为任务的习得过程中存在差异，并且在这些过程中成熟似乎对这两个亚系产生了不同的影响。此外，成年早期的B6J和B6N小鼠在嗅觉习惯化方面可能相似，但在寻求新奇事物的嗅觉方面存在差异。
