While there is a strong focus on the negative consequences of maternal immune activation (MIA) on developing brains, very little attention is directed towards potential advantages of early life challenges. In this study, we utilized a polyinosine-polycytidylic acid (poly(I:C)) MIA model to test visual pairwise discrimination (PD) and reversal learning (RL) in mice using touchscreen technology. Significant sex differences emerged in that MIA reduced the latency for males to make a correct choice in the PD task while females reached criterion sooner, made fewer errors, and utilized fewer correction trials in RL compared to saline controls. These surprising improvements were accompanied by the sex-specific upregulation of several genes critical to cognitive functioning, indicative of compensatory plasticity in response to MIA. In contrast, when exposed to a 'two-hit' stress model (MIA + loss of the social component of environmental enrichment [EE]), mice did not display anhedonia but required an increased number of PD and RL correction trials. These animals also had significant reductions of CamK2a mRNA in the prefrontal cortex. Appropriate functioning of synaptic plasticity, via mediators such as this protein kinase and others, are critical for behavioral flexibility. Although EE has been implicated in, delaying the appearance of symptoms associated with certain brain disorders, these findings are in line with evidence that it also makes individuals more vulnerable to its loss. Overall, with the right 'dose', early life stress exposure can confer at least some functional advantages, which are lost when the number or magnitude of these exposures become too great.

中文翻译：

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隐藏的天赋：Poly (I:C) 诱导的母体免疫激活以性别依赖的方式提高小鼠视觉辨别能力和逆转学习

虽然人们非常关注母体免疫激活 (MIA) 对大脑发育的负面影响，但很少关注早期生活挑战的潜在优势。在这项研究中，我们利用聚肌苷-聚胞苷酸 (poly(I:C)) MIA 模型使用触摸屏技术测试小鼠的视觉成对辨别 (PD) 和逆转学习 (RL)。显着的性别差异出现在 MIA 减少了男性在 PD 任务中做出正确选择的潜伏期，而女性则更快地达到标准，犯的错误更少，并且与盐水对照组相比，在 RL 中使用的校正试验更少。这些令人惊讶的改善伴随着几个对认知功能至关重要的基因的性别特异性上调，表明对 MIA 的补偿可塑性。相比之下，当暴露于“两次打击”压力模型（MIA + 环境丰富的社会成分 [EE] 的丧失）时，小鼠没有表现出快感缺失，但需要增加 PD 和 RL 校正试验的数量。这些动物的前额叶皮层中的 CamK2a mRNA 也显着减少。突触可塑性的适当功能，通过这种蛋白激酶等介质，对于行为灵活性至关重要。尽管 EE 与延缓某些脑部疾病相关症状的出现有关，但这些发现与它也使个体更容易受到其丧失的证据一致。总体而言，通过正确的“剂量”，早期生活压力暴露至少可以带来一些功能优势，当这些暴露的数量或幅度变得太大时，这些优势就会丧失。