Abstract
It is well established that male rats have an advantage in acquiring place-learning strategies, allowing them to learn spatial tasks more readily than female rats. However many of these differences have been examined solely during acquisition or in 24h memory retention. Here, we investigated whether sex differences exist in remote long-term memory, lasting 30d after training, and whether there are differences in the expression pattern of molecular markers associated with long-term memory maintenance. Specifically, we analyzed the expression of protein kinase M zeta (PKMζ) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA2. To adequately evaluate memory retention, we used a robust training protocol to attenuate sex differences in acquisition and found differential effects in memory retention 1d and 30d after training. Female cohorts tested for memory retention 1d after 60 training trials outperformed males by making significantly fewer reference memory errors at test. In contrast, male cohorts tested 30d after 60 training trials outperformed females of the same condition, making fewer reference memory errors and achieving significantly higher retention test scores. Furthermore, given 60 training trials, females tested 30d later showed significantly worse memory compared to females tested 1d later, while males tested 30d later did not differ from males tested 1d later. Together these data suggest that with robust training males do no retain spatial information as well as females do 24h post-training but maintain this spatial information for longer. Males also showed a significant increase in synaptic PKMζ expression and a positive correlation with retention test scores, while females did not. Interestingly, both sexes showed a positive correlation between retention test scores and synaptic GluA2 expression. Furthermore, the increased expression of synaptic PKMζ, associated with male memory but not with female memory, identifies another potential sex-mediated difference in memory processing.
Highlights
Sex differences in learning and memory function have been identified across a number of species and paradigms [1,2]
Male and female rats trained for 30 trials (Figure 1A) demonstrated significant improvement over time (F5,105 = 26.20, p
Male and female rats trained for 30 trials (Figure 1C) showed a significant decrease in reference errors over time (F5,105 = 37.89, p
Summary
Sex differences in learning and memory function have been identified across a number of species and paradigms [1,2]. Monogamous species demonstrate similar territory size for male and female pairs, thereby requiring similar predispositions for spatial navigation and memory. In polygynous species, males have larger territories than females, a predisposition identified in meadow voles, rats and humans. This interpretation has been challenged by a proposal that sex differences in spatial ability are merely side effects of testosterone, comparable to male pattern baldness and acne [2]
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