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

Episodic memory is essential to everyday life and personal identity, but its dysfunction can affect mental health. Translational animal models for investigating these dysfunctions remain limited, particularly for abnormally enhanced memories.

We developed a paradigm to induce hypermemory-like features in adult male and female rats using object recognition (OR) and object location (OL) tasks mimicking the rumination-like component of hypermemory. During odor-context association training, rats explored two identical objects with a cinnamon scent. Over the following 6h, they received 12 brief re-exposures to cinnamon odor, an odor-free stimulus, or a novel neutral odor to control for nonspecific effects. Re-exposure to the learning-associated odor was designed to promote iterative consolidation of spatial memory. After 24h, memory was assessed under odor-free conditions.

Odor re-exposure selectively enhanced OL memory in both sexes, whereas OR memory remained unaffected. Neither total object exploration nor locomotion was altered. Enhanced spatial memory was accompanied by increased ventral hippocampal c-Fos expression in both sexes.

Unlike conventional memory paradigms, which primarily assess memory impairment or enhancement, our approach models the persistence of otherwise short-term memories through repeated exposure to a learning-associated cue.

Our protocol is designed to model key features theoretically associated with hyperfunctional episodic memory, using repeated olfactory reactivation to mimic rumination and memory replay hypothesized to contribute to enhanced autobiographical memory in HSAM. This simple paradigm provides a novel translational tool for investigating the behavioral and neurobiological mechanisms underlying enhanced memory consolidation and memory persistence.