The infralimbic and prelimbic cortical areas bidirectionally regulate safety learning during normal and stress conditions.
The infralimbic and prelimbic cortical areas bidirectionally regulate safety learning during normal and stress conditions.
复制标题
边缘下和边缘前皮质区域在正常和压力条件下双向调节安全学习。
DOI：
10.1101/2023.05.05.539516
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Burgos-Robles,Anthony
中科院分区：
文献类型：
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作者：
Felix-Ortiz,AdaC;Terrell,JaelynM;Gonzalez,Carolina;Msengi,HopeD;Ramos,AngelicaR;Boggan,MirandaB;Lopez-Pesina,SavannahM;Magalhães,Gabrielle;Burgos-Robles,Anthony
安全学习是行为适应、环境适应和心理健康的关键功能。动物模型表明内侧前额叶皮层（mPFC）的边缘前区（PL）和边缘下区（IL）参与安全学习。然而，这些区域是否差异有助于安全学习，以及它们的贡献如何受到压力的影响，仍然知之甚少。在这项研究中，我们使用一种新的半自然主义小鼠模型进行威胁和安全学习。当老鼠在一个测试竞技场内导航时，它们了解到特定的区域与有害的寒冷温度（“威胁”）或舒适的温暖温度（“安全”）有关。光遗传学介导的抑制揭示了IL和PL区域在这些自然条件下选择性控制安全学习的关键作用。这种形式的安全学习也极易受到应激预暴露的影响，虽然IL抑制模仿了应激产生的缺陷，但PL抑制完全挽救了应激暴露小鼠的安全学习。总的来说，这些研究结果表明，IL和PL双向调节安全学习过程中的自然的情况下，IL区促进这一功能和PL区抑制它，特别是在压力。平衡IL和PL活动的模型被提出作为控制安全学习的基本机制。
Safety learning is a critical function for behavioral adaptation, environmental fitness, and mental health. Animal models have implicated the prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) in safety learning. However, whether these regions differentially contribute to safety learning and how their contributions become affected by stress still remain poorly understood. In this study, we evaluated these issues using a novel semi-naturalistic mouse model for threat and safety learning. As mice navigated within a test arena, they learned that specific zones were associated with either noxious cold temperatures (“threat”) or pleasant warm temperatures (“safety”). Optogenetic-mediated inhibition revealed critical roles for the IL and PL regions for selectively controlling safety learning during these naturalistic conditions. This form of safety learning was also highly susceptible to stress pre-exposure, and while IL inhibition mimicked the deficits produced by stress, PL inhibition fully rescued safety learning in stress-exposed mice. Collectively, these findings indicate that IL and PL bidirectionally regulate safety learning during naturalistic situations, with the IL region promoting this function and the PL region suppressing it, especially after stress. A model of balanced IL and PL activity is proposed as a fundamental mechanism for controlling safety learning.