Reconsolidation of episodic-like memory is affected by exposure to the predator odor TMT in mice

Abstract

When a memory is reactivated, it undergoes a reconsolidation phase, during which it becomes unstable and can be modulated. Several studies have shown that cortisol in humans and corticosterone in rodents play essential roles in learning, consolidating, and retrieving new memories. This study investigates the influence of an acute innate psychological stressor on the reconsolidation of newly acquired memories in male C57BL/6 J mice. We designed new protocols to reactivate previously learned memories in two spatial learning tasks, aiming to induce reconsolidation of hippocampus-dependent episodic-like memory and affect it through stress caused by exposure to 2,4,5-trimethylthiazoline (TMT), a chemical that mimics the scent of fox feces and induces innate fear in mice. We observed that exposure to TMT after memory reactivation impaired reconsolidation in a paradigm for one-trial spatial learning. Moreover, the glucocorticoid receptor antagonist mifepristone blocked the adverse effects of stress on reconsolidation. On the other hand, the effects of stress were not mimicked by the injection of corticosterone. Finally, stress did not affect the reconsolidation of spatial memories in the water maze task. Our results support the assumption that it is not the elevation of plasma corticosterone per se, but rather the stress context following memory reactivation, that negatively influences the reconsolidation process and subsequent memory retrieval. In conclusion, this study highlights the complexity of stress responses, which cannot be pharmacologically mimicked but require the proper behavioral and environmental context, and it provides new mouse models for investigating the reconsolidation of spatial memories.