Females, but not males, require protein degradation in the hippocampus for contextual fear memory formation

Strong evidence supports a role for protein degradation in fear memory formation. However, these data have been largely done in only male animals. Here, we found that following contextual fear conditioning, females, but not males, had increased levels of proteasome activity and K48 polyubiquitin protein targeting in the dorsal hippocampus, the latter of which occurred at chaperones or RNA processing proteins. In vivo CRISPR-dCas9-mediated repression of protein degradation in the dorsal hippocampus impaired contextual fear memory in females, but not males. These results suggest a sex-specific role for protein degradation in the hippocampus during the consolidation of a contextual fear memory.

Automated summary

Evidence suggests that protein degradation plays a significant role in fear memory formation, particularly in the dorsal hippocampus of female animals. Inhibiting protein degradation in this region impairs contextual fear memory consolidation in females specifically, highlighting a sex-specific mechanism in fear memory processes.