A novel behavioral paradigm to model hypermemory-like features in rats

Abstract

Episodic memory is essential to everyday life and personal identity. However, its dysfunctions can profoundly affect mental health, and translational methods for investigating them in animals remain limited. Most rodent paradigms focus on memory deficits, whereas few tools model abnormally enhanced and persistent memories. Here, we developed a behavioral paradigm to induce hypermemory-like features in adult male and female rats using a version of object recognition (OR) and object location (OL) tasks specifically modified to mimic the rumination-like component of hypermemory. During the odor-context association training, rats explored two identical objects in the presence of a cinnamon scent. Over the following 6 h, they received 12 brief re-exposures in their home cage to either the cinnamon odor or an odor-free stimulus. By repeatedly reactivating the memory trace, these re-exposures promoted its hyperconsolidation without re-exposing animals to the original context or objects. Twenty-four hours later, memory was assessed under odor-free conditions. Odor re-exposure selectively enhanced OL memory in rats of both sexes, whereas OR memory remained unaffected. The procedure did not alter total object exploration or locomotor activity. Enhanced spatial memory was also accompanied by increased c-Fos expression in the ventral hippocampus in both sexes. Our protocol recapitulates key features observed in individuals with hyperfunctional episodic memory: continuous memory reactivation and rumination which may contribute to the excessive strengthening and persistence of specific memories. This simple and reproducible paradigm provides a novel translational tool for investigating the behavioral and neurobiological mechanisms underlying memory hyperconsolidation and maladaptive memory persistence.