Dos Santos Corrêa Moisés, Grisanti Gabriel David Vieira, Franciscatto Isabelle Anjos Fernandes, Tarumoto Tatiana Suemi Anglas, Tiba Paula Ayako, Ferreira Tatiana Lima, Fornari Raquel Vecchio
Center for Mathematics, Computing and Cognition (CMCC), Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.
Neurobiol Stress. 2022 May 9;18:100459. doi: 10.1016/j.ynstr.2022.100459. eCollection 2022 May.
The ability to retrieve contextual fear memories depends on the coordinated activation of a brain-wide circuitry. Transition from recent to remote memories seems to involve the reorganization of this circuitry, a process called systems consolidation that has been associated with time-dependent fear generalization. However, it is unknown whether emotional memories acquired under different stress levels can undergo different systems consolidation processes. Here, we explored the activation pattern and functional connectivity of key brain regions associated with contextual fear conditioning (CFC) retrieval after recent (2 days) or remote (28 days) memory tests performed in rats submitted to strong (1.0 mA footshock) or mild (0.3 mA footshock) training. We used brain tissue from Wistar rats from a previous study, where we observed that increasing training intensity promotes fear memory generalization over time, possibly due to an increase in corticosterone (CORT) levels during memory consolidation. Analysis of Fos expression across 8 regions of interest (ROIs) allowed us to identify coactivation between them at both timepoints following memory recall. Our results showed that strong CFC elicits higher Fos activation in the anterior insular and prelimbic cortices during remote retrieval, which was positively correlated with freezing along with the basolateral amygdala. Rats trained either with mild or strong CFC showed broad functional connectivity at the recent timepoint whereas only animals submitted to the strong CFC showed a widespread loss of coactivation during remote retrieval. Post-training plasma CORT levels are positively correlated with FOS expression during recent retrieval in strong CFC, but negatively correlated with FOS expression during remote retrieval in mild CFC. Our findings suggest that increasing training intensity results in differential processes of systems consolidation, possibly associated with increased post-training CORT release, and that strong CFC engages activity from the aIC, BLA and PrL - areas associated with the Salience Network in rats - during remote retrieval.
检索情境恐惧记忆的能力取决于全脑神经网络的协同激活。近期记忆向远期记忆的转变似乎涉及该神经网络的重组，这一过程称为系统巩固，它与时间依赖性恐惧泛化有关。然而，尚不清楚在不同应激水平下获得的情绪记忆是否会经历不同的系统巩固过程。在此，我们探究了在经历强烈（1.0毫安足部电击）或温和（0.3毫安足部电击）训练的大鼠中，在近期（2天）或远期（28天）记忆测试后，与情境恐惧条件反射（CFC）检索相关的关键脑区的激活模式和功能连接性。我们使用了先前一项研究中的Wistar大鼠脑组织，在该研究中我们观察到，随着时间的推移，增加训练强度会促进恐惧记忆的泛化，这可能是由于记忆巩固过程中皮质酮（CORT）水平的升高。对8个感兴趣区域（ROI）的Fos表达进行分析，使我们能够确定记忆回忆后两个时间点它们之间的共激活情况。我们的结果表明，强烈的CFC在远期检索期间在前岛叶和前额叶皮质引发更高的Fos激活，这与僵立以及基底外侧杏仁核呈正相关。接受温和或强烈CFC训练的大鼠在近期时间点显示出广泛的功能连接，而只有接受强烈CFC训练的动物在远期检索期间表现出共激活的广泛丧失。训练后血浆CORT水平在强烈CFC的近期检索期间与FOS表达呈正相关，但在温和CFC的远期检索期间与FOS表达呈负相关。我们的研究结果表明，增加训练强度会导致不同的系统巩固过程，这可能与训练后CORT释放增加有关，并且强烈的CFC在远期检索期间会激活大鼠中与显著网络相关的前岛叶皮质、基底外侧杏仁核和前额叶皮质区域的活动。
