Sex-specific exploration patterns and noradrenergic modulation in object recognition memory: Role of the perirhinal...

Object recognition memory (ORM) relies on two processes: familiarity, mediated by the perirhinal cortex (PRH), and recollection, supported by the hippocampus (HIP). These processes are recruited depending on memory strength: brief exploration forms weak traces relying on PRH familiarity, whereas extended exploration produces strong traces requiring HIP recollection. Noradrenaline (NA) modulates these mechanisms via β2-adrenergic receptors (β2-AR), influencing memory strength and consolidation. However, whether this modulation differs between sexes under conditions generating weak versus strong memory traces remains unknown. We examined how NA and β2-AR influence ORM in male and female mice under these conditions.

Swiss mice were tested in the Novel Object Recognition task using training durations of 1-10 min and delays of 24-48 h. Atomoxetine (ATO) was used to increase NA levels, and ICI-118,551 (ICI) to block β2-AR. Neural activation was assessed via c-Fos immunohistochemistry in PRH and HIP.

Females showed greater efficiency in object processing, requiring less exploration than males. Under weak training conditions, ATO facilitated the formation of long-term ORM in females but not in males, accompanied by increased PRH c-Fos expression without HIP involvement. β2-AR blockade impaired ORM acquisition only in females, with no significant changes in c-Fos. In males, performance depended on object dissimilarity; increased NA did not enhance ORM unless stimuli were highly distinct.

These findings reveal sex differences in noradrenergic modulation of ORM. In females, NA acting via β2-AR supports memory formation through PRH-dependent familiarity, emphasizing the importance of sex as a biological variable in research.