Department of Animals in Science and Society, Division of Animal Welfare and Laboratory Animal Science, Utrecht University, Utrecht, The Netherlands.
Behav Brain Res. 2013 Jun 1;246:1-9. doi: 10.1016/j.bbr.2013.02.023. Epub 2013 Feb 28.
Our recent studies revealed a profound impairment to habituate in 129P3 mice compared to BALB/c mice after repeated exposure to an initially novel environment. This was accompanied by strain-specific c-Fos expression in the prelimbic cortex, a brain area related to emotional and cognitive processing. The metabotropic glutamate receptor 5 (mGlu5R) antagonist MPEP increased c-Fos expression in brain areas related to cognition while it decreased c-Fos expression in brain areas processing emotions in 129P3 animals. We hypothesised that the non-adaptive response of 129P3 mice to a novel environment may be the result of impaired neural processing between the prelimbic cortex and emotion processing brain areas, possibly regulated by glutamatergic neurotransmission. To explore this hypothesis, we compared c-Fos activity in between naïve and repeatedly tested animals. Further, we investigated mRNA expression of CRFR1 and mGlu5R in the prelimbic cortex and amygdala, since these transmitter systems are not only involved in the regulation of anxiety, but are indicated to be co-expressed in relevant brain areas. Behavioural results confirmed strain-specific habituation profiles and strain-specific c-Fos expression in brain areas regulating cognitive and emotional processes in BALB/c and 129P3 mice. We found that repeated testing resulted in contrasting behavioural responses in both strains, and this was accompanied by strain-specific effects on c-Fos and receptor-expression. From these results it may be concluded that habituation in BALB/c mice reflects a shift from a primary emotional response to a more cognitively controlled behaviour, and that this shift over time may be impaired in 129P3 animals.
我们最近的研究表明，与 BALB/c 小鼠相比，129P3 小鼠在反复暴露于最初新颖的环境后，习惯形成能力受到严重损害。这伴随着在外侧前额皮质（与情绪和认知处理相关的大脑区域）中出现特定于品系的 c-Fos 表达。代谢型谷氨酸受体 5（mGlu5R）拮抗剂 MPEP 在 129P3 动物中增加了与认知相关的大脑区域的 c-Fos 表达，同时减少了处理情绪的大脑区域的 c-Fos 表达。我们假设 129P3 小鼠对新环境的非适应性反应可能是外侧前额皮质和情绪处理大脑区域之间神经处理受损的结果，这可能受到谷氨酸能神经传递的调节。为了探索这一假设，我们比较了初次测试和反复测试动物之间的 c-Fos 活性。此外，我们还研究了外侧前额皮质和杏仁核中 CRFR1 和 mGlu5R 的 mRNA 表达，因为这些递质系统不仅参与了焦虑的调节，而且还表明在相关的大脑区域中共同表达。行为学结果证实了 BALB/c 和 129P3 小鼠中存在特定于品系的习惯形成模式和大脑区域中调节认知和情绪过程的特定于品系的 c-Fos 表达。我们发现，反复测试导致两种品系均出现了截然不同的行为反应，并且伴随着 c-Fos 和受体表达的特定于品系的影响。从这些结果可以得出结论，BALB/c 小鼠的习惯形成反映了从主要的情绪反应到更具认知控制的行为的转变，并且这种随时间的转变可能在 129P3 动物中受损。
