Remote contextual fear retrieval engages activity from salience network regions in rats

Moisés Dos Santos Corrêa; Gabriel David Vieira Grisanti; Isabelle Anjos Fernandes Franciscatto; Tatiana Suemi Anglas Tarumoto; Paula Ayako Tiba; Tatiana Lima Ferreira; Raquel Vecchio Fornari

doi:10.1016/j.ynstr.2022.100459

Remote contextual fear retrieval engages activity from salience network regions in rats

Neurobiol Stress. 2022 May 9:18:100459. doi: 10.1016/j.ynstr.2022.100459. eCollection 2022 May.

Authors

Moisés Dos Santos Corrêa¹, Gabriel David Vieira Grisanti¹, Isabelle Anjos Fernandes Franciscatto¹, Tatiana Suemi Anglas Tarumoto¹, Paula Ayako Tiba¹, Tatiana Lima Ferreira¹, Raquel Vecchio Fornari¹

Affiliation

¹ Center for Mathematics, Computing and Cognition (CMCC), Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.

Abstract

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.

Keywords: Anterior insular cortex; Basolateral amygdala; Prelimbic cortex; Stress; Systems consolidation.