Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
Master's Program in Cognitive Science, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Int J Mol Sci. 2023 Oct 13;24(20):15143. doi: 10.3390/ijms242015143.
Observational fear-learning studies in genetically modified animals enable the investigation of the mechanisms underlying the social transmission of fear-related information. Here, we used a three-day protocol to examine fear conditioning by proxy (FCbP) in wild-type mice (C57BL/6J) and mice lacking the β2-subunit of the nicotinic acetylcholine receptor (nAChR). Male animals of both genotypes were exposed to a previously fear-conditioned (FC) cage mate during the presentation of the conditioned stimulus (CS, tone). On the following day, observer (FCbP) mice were tested for fear reactions to the tone: none of the β2-KO mice froze to the stimulus, while 30% of the wild-type mice expressed significant freezing. An investigation of the possible factors that predicted the fear response revealed that only wild-type mice that exhibited enhanced and more flexible social interaction with the FC cage mate during tone presentations (Day 2) expressed fear toward the CS (Day-3). Our results indicate that (i) FCbP is possible in mice; (ii) the social transmission of fear depends on the interaction pattern between animals during the FCbP session and (iii) β2-KO mice display a more rigid interaction pattern compared to wild-type mice and are unable to acquire such information. These data suggest that β2-nAChRs influence observational fear learning indirectly through their effect on social behaviour.
在遗传修饰动物中进行观察性恐惧学习研究，可以调查恐惧相关信息的社会传递背后的机制。在这里，我们使用了三天的方案来检查野生型小鼠（C57BL/6J）和缺乏烟碱型乙酰胆碱受体（nAChR）β2 亚基的小鼠的间接恐惧条件作用（FCbP）。两种基因型的雄性动物在呈现条件刺激（CS，音调）时，都暴露于先前已进行过恐惧条件作用（FC）的笼伴中。在第二天，观察者（FCbP）小鼠接受对音调的恐惧反应测试：没有一只β2-KO 小鼠对刺激冻结，而 30%的野生型小鼠表现出明显的冻结。对可能预测恐惧反应的因素的调查表明，只有在音调呈现期间与 FC 笼伴表现出增强和更灵活的社交互动的野生型小鼠，才会对 CS（第三天）表现出恐惧。我们的结果表明：（i）FCbP 在小鼠中是可能的；（ii）恐惧的社会传递取决于 FCbP 期间动物之间的相互作用模式；（iii）β2-KO 小鼠与野生型小鼠相比表现出更僵化的相互作用模式，并且无法获得此类信息。这些数据表明，β2-nAChRs 通过其对社交行为的影响间接影响观察性恐惧学习。
