Sex-related differences in somatic plasticity and possible role of ERK1/2: An in-vivo study of young-adult rats

•Low frequency stimulation (LFS) was induced LTD more easly in female rats than male rats.•Activity-dependent down-regulation of MAPK3 and MAPK14 may be a novel mechanism of LTD in young-female rats.•The increased ERK1/2 activation may lead to failed LTD in young-male rats. The present study investigates sex differences in hippocampal functions in the context of synaptic plasticity, which is the cellular basis of learning and memory, and differences in the mitogen-activated protein kinase (MAPK) pathway that accompanies plasticity in young-adult rats. The long-term potentiation (LTP) and long-term depression (LTD) were induced by stimulating the perforant pathway (PP) and field potentials composed of the field excitatory post-synaptic potential (fEPSP) and population spike (PS) were recorded from the dentate gyrus (DG). Following the completion of the electrophysiological recordings, the hippocampi were removed bilaterally, and the protein and gene expression levels of the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and P38-MAPK were determined by Western blot analysis and real-time PCR, respectively. No significant difference was found in synaptic and neuronal function before (basal) and after high-frequency stimulation between male and female rats. Nevertheless, female, but not male, rats were able to express long term depression at the PP – DG synapses, suggesting that sex differences in plasticity are stimulation paradigm specific. MAPK1 expression was higher in males and MAPK3 expression was higher in females, but these differences disappeared after induction of plasticity in both sexes. While the expression of MAPK8 is influenced by sex, independent of the induction of plasticity, MAPK14 expression was down regulated by plasticity induction in females, but not males. No effect of sex, HFS and LFS on total and phosphorylated levels of MAPKs was found except phosphorylated ERK1/2. Phosphorylation of ERK1/2 was up regulated after LFS in male rats but did not change in female rats. These findings indicate that LFS-induced plasticity is differentially modulated between sexes, probably as a result of increased activation of ERK1/2 in male rats.