Sex differences in physical skill learning with consequences for neurogenesis and cell survival in the hippocampus
Creators: name: DiFeo, Gina
Publisher: name: No Publisher Supplied
Year: 2016

description: In animal models of learning it has been proposed that males and females use different pathways to perform particular behaviors and thus perform differently on a variety of training tasks. These sex differences in performance and learning have consequences for numerous measures of plasticity and brain function. The dentate gyrus (DG) of the adult hippocampus gives rise to thousands of new neurons every day, yet a majority of these cells die off within one to two weeks of their birth. Our laboratory has previously reported that learning increases the number of new neurons in the brain by rescuing them from death. These new neurons are capable of being rescued from apoptosis using the accelerating rotarod, a physical skill learning task, in adult male rats. In the first experiment here, we tested the hypothesis that a modified version of this task, which increases motivation, will rescue a greater number of new cells than training with the traditional motor skill task. We trained adult male and female rats on the standard rotarod and the modified â€œmotirodâ€  task. The trained males successfully learned their respective tasks and retained significantly more new cells in the DG than untrained males. On the other hand, females performed better on the motirod than they did on the rotarod, and thus, female trained on the motirod retained a significantly greater number of cells than females trained on the rotarod and untrained females. To our knowledge this was the first demonstration of sex differences in performance on the rotarod and motirod, both gross motor skill tasks. In the second experiment we performed the same procedures as in the first but examined pubescent males and females. The trained pubescent males and females successfully learned both tasks and as a result rescued significantly more newly born DG cells than untrained animals. The data did not indicate any sex differences in learning the tasks, which is in agreement with the literature stating that many sex differences in learning tend to emerge after puberty.    Adolescence, and, more importantly, the impact of stress during adolescence, is the least studied of the developmental stages of life. Sexual aggression during the adolescent years is one of the most traumatic and stressful of life experiences and approximately 30% of young women worldwide are the victims of such abuse. In the third set of experiments we employed a novel animal model developed in our laboratory that mimics early life trauma in pubescent female rodents. We developed this animal model in order to examine the effects of this type of aggressive stress experienced by adolescent women hereafter known as Sexual Conspecific Aggressive Response (SCAR). During the SCAR experience females were repeatedly exposed to an aggressive adult male for 30 minutes every third day throughout pubescence in order to mimic chronic stress and we examined how this impacted future learning on the motirod task. We also examined the effects of motirod training on cell survival in the DG of the hippocampus in these same female animals. There were no differences in learning the motirod task between pubescent females exposed to an adult male during pubescence and those that were not. However, the SCAR animals rescued significantly less newly born DG cells as a result of training compared to NO SCAR animals. There were also no differences discovered between the SCAR and No SCAR females in either cell proliferation or cell survival in the DG. Based on our behavioral and hormone analyses, the SCAR experience was indeed stressful to the females that were exposed to the adult males during adolescence. Our findings that the SCAR animals were not susceptible to the positive effects of learning on cell survival are particularly interesting because the majority of research has demonstrated that successful learning increases the retention of newly born cells in the DG and rescues them from cell death. It is likely that the stress of the SCAR procedures interacted in a complex manner with the effects of learning and cell survival. Future research on the interplay among stress, neurogenesis and learning will be necessary to elucidate our findings as well as designing experiments that include both males and females in order to better understand the impact early life stress and vulnerability to certain psychological disorders. Our SCAR model will serve as a useful tool in order to better understand how the female brain responds to sexual trauma and aggression that occurs during pubescence. Our model could ultimately lead to clinical interventions for young women who have experienced the severely detrimental trauma caused by sexual abuse and aggression.