Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats

Abstract

Background Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. Results In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. Conclusions Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.

Sex Differences in Spatial Learning and Memory in Valproic Acid Rat Model of Autism: Possible Beneficial Role of Exercise Interventions

“…In the case of MWM reference memory, we did not observe a sex difference between VPA-exposed male and female offspring. However, here and in our previous study ( Safari et al, 2021 ), we saw a sex difference between male and female control rats. Both IT and CT exercises in both control and VPA-exposed male rats significantly improved MWM acquisition.…”

“…In our previous work ( Safari et al, 2021 ), we discussed the underlying mechanisms for sex differences in male and female control animals (male control rats outperformed female control rats). However, here we found that VPA-exposed female offspring had a better performance than VPA-exposed male offspring (unlike control animals where male offsprings performed better).…”

Sprague-Dawley rats differ in responses to medial perforant path paired pulse and tetanic activation as a function of sex and age

“…The greater normalized LTP in adult male than adult female rats ( Supplemental Figure S2 ) replicates Maren 12 . Higher levels of excitability in the MPP circuit of female rats than male rats are seen in data sets from earlier studies 13 (raw data shared by Safari and Karimi 2021), but see 14 for counter example.…”

Behavioral and Synaptic Phenotypes of Female Prdx6−/− Mice

“…The open field test was used to measure the locomotion function based on their spontaneous exploratory behavior in an open field maze ( Figure 2 A) [ 19 , 20 ]. The female Prdx6 −/− mice showed no significant difference in the total distance traveled ( Figure 2 B) [ U = 25, p = 0.171] and moving speed ( Figure 2 C) [ t 16 = 1.614, p = 0.126] compared with Prdx6 +/+ mice after 10 min of exploration.…”

“…In addition, it appears to regulate emotional response and spatial memory formation in male mice [ 8 ]. Therefore, whether the Prdx6 gene influences stress-coping mechanisms [ 17 , 18 ] and memory performance [ 19 ] in females is intriguing. Thus, in the present study, we investigated the function of PRDX6 in the synaptic and behavioral phenotypes of female mice.…”