Sex Differences in Hippocampal Long-Term Depression and the N-Methyl-DAspartate Receptor in Rats - Positive Correlation between LTD and Glun2b Subunit

Background: Numerous studies have suggested that sexual dimorphism may exist in learning and memory. Herein, we associated sex differences in the long-term potentiation (LTP) and the long-term depression (LTD) with the N-methyl-D-aspartate (NMDA) receptor subunits, given their well-known roles in the establishment of longterm memory. Methods: After a 15-min baseline recording, LTP and LTD were induced by application of high- and low- frequency stimulation protocols, respectively. The averages of the excitatory postsynaptic potential (EPSP) slopes and population spike (PS) amplitudes between 70-75 minutes were used as a measure of the LTP/LTD. The mRNA level of GluN1, GluN2A and GluN2B subunits were evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Results: Male and female rats showed no differences in a pre-LTP and pre-LTD I/O curves. Although the magnitude of LTP was similar between sexes, female animals exhibited LTD in much more easily than their male counterparts in the absence of the difference in I/O curves. Concomitantly, none of transcript significantly differed between sexes for baseline gene expression, while the decreasing NR2A/NR2B ratio in female rats throughout LTP and LTD time courses was only observed after LTP in male rats. In addition, NR1 mRNA expression was increased in male rats compared to female rats 60- min after LTP induction. Conclusion: The capacity for LTD expression is higher in female rats compared to male rats in young adult ages, and this sex difference is paralleled by a sex difference in GluN2B subunit generated by perforant path LFS. The present study suggests that sex differences in hippocampus-dependant learning tasks may be result of sexually dimorphic hippocampal LTD, but not LTP.