Lets talk about sex: Male and female mice show similar fear memory retention despite hippocampal activity differences during encoding and consolidation

Abstract

Accurate and efficient memory processing is essential for survival. A body of ongoing work in both human subjects and animal models suggests that memory processing may differ substantially between males and females. In mice, contextual fear memory (CFM) encoding, consolidation, and recall have been well studied, and the mouse hippocampus and amygdala have been implicated in these processes. The present study addresses whether the activation of these brain regions differs between male and female mice at each stage of CFM processing. We find that male and female C57BL6 mice show no differences in sleep behavior following single-trial contextual fear conditioning (CFC), which is essential for CFM consolidation. We also find no significant differences in CFM recall behavior between male and female mice. However, females - but not males - show significantly increased expression of cFos in dorsal hippocampal CA1 and CA2 neurons during CFM encoding. On the other hand, males - but not females - show increased cFos expression among dentate gyrus (DG) granule cells, and decreased cFos expression within dorsal CA1 and CA3 during CFM consolidation. Males also show significant decreases in dorsal CA1 cFos expression during memory recall. These findings highlight the idea that the neurobiological underpinnings of memory processing may differ between males and females, even when recall performance is identical. HighlightsHistorically, research on the neurobiological basis of memory processing has been carried out mainly in male subjects. Thus, our understanding of these mechanisms is biased towards male brain neurophysiology. This is problematic, as numerous studies have reported sex-based performance differences for episodic memory tasks, in which male subjects have variously performed better, worse, or the same as females. Here, we find that male and female mice perform similarly on a well-studied experimental memory task but nonetheless have differences in the relative activity of different brain structures during sequential stages of memory processing. This emphasizes the importance of including both males and females in memory studies, due to potential sex differences in the neurobiological substrates of memory.