Sex Differences In Spatial Learning Research Articles

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

In the current study, we first tried to determine sex differences in spatial learning and memory in the valproic acid (VPA) rat model of autism. Second, the effects of interval training (IT) and continuous training (CT) exercises were examined in male and female offsprings. To induce autism-like animal model, the pregnant rats were injected 500 mg/kg NaVPA (intraperitoneal) at the embryonic day 12.5. IT and CT aerobic exercises were started at postnatal day 56. Then, on postnatal days 84–89, a Morris water maze (MWM) test was conducted on the separate groups of offsprings. Aerobic training was performed on a rodent treadmill with 0% slope for 8 weeks, 5 days/week, and 50 min/day. Unlike control animals, VPA-exposed female offspring had a better performance than VPA-exposed male offspring in MWM acquisition. In the case of MWM reference memory, we did not observe a sex difference between VPA-exposed male and VPA-exposed female offspring. Both IT and CT exercises in both control and VPA-exposed male rats significantly improved MWM acquisition. Moreover, both IT and CT exercises significantly improved MWM acquisition in control female rats. In addition, IT exercise (but not CT) significantly improved MWM acquisition in VPA-exposed female offsprings. Both IT and CT exercises in VPA-exposed that male and female offsprings improved the MWM reference memory. In conclusion, our observation demonstrated that prenatal exposure to VPA affects the spatial learning and memory in a sex dependent manner. We have shown that both IT and CT exercises are able to improve cognitive function in healthy and autistic rat offsprings.

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

BackgroundRecent 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.ResultsIn 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.ConclusionsTaken 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 learning and memory following short-term dietary restriction in the rat

IntroductionAcute or prolonged dietary restriction has been shown to have significant effects on learning and memory, and also on the food seeking behaviour in animals. AimThis study investigated whether or not there are sex differences in spatial learning and memory following short-term dietary restriction in the rat. MethodsTwo month-old male (n=24) and female (n=24) Sprague-Dawley rats were randomly assigned to either (1) male or female control (i.e. normal diet regimen); (2) male or female 40% dietary restriction for either 2hours (2h-DR) or 2 weeks (2 wks-DR) duration. Following the restriction paradigm (i.e. either 2h or 2 weeks), animals were weighed, and learning and memory was assessed daily for a total of 5 days by Morris Water Maze. ResultsDietary restriction for 2h provoked high speed swimming in female rats compared to controls. However the females performance in water maze was inferior to the control animals. Two weeks after 40% DR resulted in reduction of male's body weight by 20% compared to their control group. However, both males and females showed difficulties in water maze learning and memory test after the 2 weeks 40% DR. The animals swam longer distance and took longer time to reach the platform when compared to their age-matched controls. ConclusionIn fully developed brain, adult animal's cognitive performance is shown to be affected by acute and prolonged stress in the form of food restriction. Interestingly, the impact of this stress was different according to the sex of the animals. In female rats, dietary restriction has a negative effect on learning and memory after 2h and 2 weeks intervals. In male rats, 2h of DR has a positive effect on learning and memory; however this effect is not maintained and by 2 weeks there is a negative effect similar to that seen in female animals.

Do hormonal changes that appear at the onset of puberty determine the strategies used by female rats when solving a navigation task?

The present set of experiments evaluated the possibility that the hormonal changes that appear at the onset of puberty might influence the strategies used by female rats to solve a spatial navigation task. In each experiment, rats were trained in a triangular shaped pool to find a hidden platform which maintained a constant relationship with two sources of information, one individual landmark and one corner of the pool with a distinctive geometry. Then, three test trials were conducted without the platform in counterbalanced order. In one, both the geometry and the landmark were simultaneously presented, although in different spatial positions, in order to measure the rats' preferences. In the remaining test trials what the rats had learned about the two sources of information was measured by presenting them individually. Experiment 1, with 60-day old rats, revealed a clear sex difference, thus replicating a previous finding (Rodríguez et al., 2010): females spent more time in an area of the pool that corresponded to the landmark, whereas males spent more time in the distinctive corner of the pool even though the remaining tests revealed that both sexes had learned about the two sources of information. In Experiment 2, 30-day old female rats, unlike adults, preferred to solve the task using the geometry information rather than the landmark (although juvenile males behaved in exactly the same way as adults). Experiment 3 directly compared the performance of 90- and 30-day old females and found that while the adult females preferred to solve the task using the landmark, the reverse was true in juvenile females. Experiment 4 compared ovariectomized and sham operated females and found that while sham operated females preferred to solve the task using the landmark, the reverse was true in ovariectomized females. Finally, Experiment 5 directly compared adult males and females, juvenile males and females, and ovariectomized females and found that adult males, juvenile males and females, and ovariectomized females did not differ among them in their preferred cue, but they all differed from adult females.

Sex-specific influence of exposure to bisphenol-A between adolescence and young adulthood on mouse behaviors

Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters and has a wide range of effects on central nervous system. Adolescence is another important developmental period besides the early critical prenatal and neonatal periods. In the present study, we exposed mice to BPA (40, 400 μg/kg/d) between adolescence and young adulthood for 8 weeks and investigated its effects on the non-reproductive behaviors. In open field tests, rearing and grooming sex differences were abolished by BPA exposure. In the elevated plus maze test, the number of open arm entries, the time spent in open arms, and the number of unprotected head dips in the center area were reduced in males but increased in females by BPA at 40 or 400 μg/kg/d, thus eliminating or reversing sex differences in these behaviors. In the Morris water maze task, exposure to BPA at 40 μg/kg/d significantly extended the average escape pathlength to the hidden platform in males, but no significant influence was found in females; thus, the sex differences in spatial learning and memory were abolished. In the step-down test, the latency to step down from the platform 24 h after receiving a footshock was shortened by BPA exposure in males but not in females; thus, a sex difference was induced in passive avoidance memory in mice. These results suggest that long-term exposure to low levels of BPA between adolescence and young adulthood alters characteristic differences in certain non-reproductive behaviors of males and females, including exploration, anxiety, spatial learning and memory, and passive avoidance memory, although no obvious changes were found in the serum hormone levels or in the weights of reproductive organs.

Spatial learning abilities in males and females of the subterranean rodent Ctenomys talarum

Few studies have focused on sex differences in spatial learning in subterranean rodents. Ctenomys talarum inhabits complex burrow systems, with males occupying larger areas than females. We assessed spatial learning ability by measuring the capacity of C. talarum individuals to solve appetitive radial or longitudinal spatial tasks during the non-reproductive season. We found that, regardless of sex differences in home-range size, males and females performed similarly in both tasks, rapidly improving their spatial performance after the initial trials and maintaining an accurate performance during subsequent trials. Our results show that sex differences in home-range sizes may not always lead to the evolution of sexually dimorphic spatial abilities.

Sex-specific strategies in spatial orientation in C57BL/6J mice

Sex differences in spatial learning are found in many species of mammals and even in invertebrates. Results from laboratory mouse studies, however, have been inconsistent in comparison to studies of humans, laboratory rats and wild rodent species. Here we re-examined this question in C57BL/6J mice that were exposed to enriched environments using two tasks, an object recognition task and a place learning task where mice were motivated by exploratory drive, not aversive conditioning or food restriction. Using these methods, we found a female advantage for object recognition, similar to the female advantage found in humans and laboratory rats. In the place learning task, male performance was unimpaired by intra-maze cue deletion but impaired by extra-maze cue masking. Female mice, in contrast, were able to navigate accurately under both cue conditions. In summary, by utilizing testing and housing methods that were more species appropriate, we found sex-specific patterns of cue encoding and place learning in better accordance with prior results from other mammalian species. The implication of these results is that the C57BL/6J mouse is an appropriate model for the study of cognitive sex differences in mammals.

Nicotinic α7- or β2-containing receptor knockout: Effects on radial-arm maze learning and long-term nicotine consumption in mice

Classically, it has been thought that high-affinity nicotinic receptors-containing β2 subunits are the most important receptor subtypes for nicotinic involvement in cognitive function and nicotine self-administration, while low affinity α7-containing nicotinic receptors have not been thought to be important. In the current study, we found that knockout of either β2 or α7 subunits caused significant deficits in spatial discrimination in mice. The character of the impairment in the two knockouts was different. The β2 knockout preferentially impaired cognition in males while the α7 caused impairment regardless of sex. Both β2- and α7-containing nicotinic receptors also are important for nicotine self-administration, also in different ways. Most animal model studies of nicotine self-administration are relatively short-term whereas the problem of tobacco addiction is considerably longer-term. To better model the impact of nicotinic receptor subtypes on nicotine self-administration over the long-term, we studied the impact of genetic knockout of low affinity α7 receptors vs. high-affinity β2-containing nicotinic receptors. Mice with knockouts of either of these receptors and their wildtype counter parts were given free access to a choice of nicotine-containing and nicotine-free solution in their home cages on a continuous basis over a period of 5 months. During the first few weeks, the β2-containing nicotinic receptor knockout mice showed a significant decrease in nicotine consumption relative to wildtype mice, whereas the α7 knockout mice did not significantly differ from wildtype controls at the beginning of their access to nicotine. Interestingly, in the longer-term after the first few weeks of nicotine access, the β2 knockout mice returned to wildtype mouse levels of nicotine consumption, whereas the α7 knockout mice developed an emergent decrease in nicotine consumption. The α7 receptor knockout-induced decrease in nicotine consumption persisted for the 5-month period of the study. Both α7- and β2-containing nicotinic receptors play critical roles in cognitive function and nicotine self-administration. Regarding cognitive function, β2-containing receptors are important for maintaining normal sex differences in spatial learning and memory, whereas α7 receptors are important for cognitive function regardless of sex. Regarding nicotine self-administration high-affinity β2-containing nicotinic receptors are important for consumption during the initial phase of nicotine access, but it is the α7 nicotinic receptors that are important for the longer-term regulation of nicotine consumption.

Sex differences in visual-spatial learning using a virtual water maze in pre-pubertal children

Gonadal steroid effects during puberty are often hypothesized to account for the male advantage seen in certain spatial tasks. One spatial task where males consistently show better performance than females is the Morris Water Task in which subjects must navigate to a goal location in a pool. We examined whether sex differences exist in pre-pubertal children completing a Virtual Morris Water Task, which has previously shown strong sex differences in adults. Pre-pubertal boys show superior performance to similar-aged girls, as evidenced by shorter latencies to find the platform and stronger preferences for the platform location during a probe trial. These results suggest that sex differences in spatial learning and memory exist prior to puberty and do not appear to require the effects of sex hormones at puberty. Rather, these differences may reflect early-life hormonal effects on hippocampal-dependent processes and may suggest different preferential learning strategies by boys and girls.

Age-related sex differences in spatial learning and basal forebrain cholinergic neurons in F344 rats

Basal forebrain cholinergic neurons are important for spatial learning in rodents. Spatial learning ability is reportedly better in males than females, and declines with age. To examine the role of cholinergic function in sex- or age-related differences in spatial learning, we compared the size of basal forebrain cholinergic neurons (BFCN) of young and aged male and female Fischer 344 (F344) rats that had been trained in the Morris water maze. Young male and female rats were equally proficient in finding the platform during training trials, but probe tests revealed that young male rats had better knowledge of the platform's precise location. Impairments in spatial learning were observed in aged rats, and the advantage of males over females was lost. BFCN were significantly larger in young male than young female rats, and were correlated with spatial memory performance for both groups. BFCN were smaller in aged than young males; no change was seen between young and aged females. In the groups of aged rats the correlation between neuron size and spatial memory was lost. The present findings provide further evidence of a role for the basal forebrain cholinergic system in spatial learning, but reveal a complex interaction between sex, age and behavioral performance.

Unpacking the cognitive map: the parallel map theory of hippocampal function.

In the parallel map theory, the hippocampus encodes space with 2 mapping systems. The bearing map is constructed primarily in the dentate gyrus from directional cues such as stimulus gradients. The sketch map is constructed within the hippocampus proper from positional cues. The integrated map emerges when data from the bearing and sketch maps are combined. Because the component maps work in parallel, the impairment of one can reveal residual learning by the other. Such parallel function may explain paradoxes of spatial learning, such as learning after partial hippocampal lesions, taxonomic and sex differences in spatial learning, and the function of hippocampal neurogenesis. By integrating evidence from physiology to phylogeny, the parallel map theory offers a unified explanation for hippocampal function.

Sex difference and laterality in the volume of mouse dentate gyrus granule cell layer

Sex differences in spatial learning have been reported in both humans and rodents. Correspondingly, there have been reports of sexual dimorphism in the morphology of the hippocampal formation (HF), a brain structure implicated in spatial cognition. In Experiment 1, we confirmed earlier reports that the overall volume of the granule cell layer (GCL) of the dentate gyrus (DG) of A/J mice is larger in males than in females. We also found that male A/J mice have a larger GCL volume in the right hemisphere than the left. Female A/J mice displayed no such laterality. A similar pattern of laterality, favoring the right HF, had been reported previously in male, but not female, rats. In Experiment 2, we examined mice with a defective structural gene for androgen receptors ( testicular feminization mutant, or tfm mice) on a C57/BL6J background. The C57/J strain had not previously been examined for hippocampal sexual dimorphism. We found no sexual dimorphism in the left, right, or total volume of the GCL in C57/BL6J mice whether they were wildtype or tfm. However, the right GCL volume was greater than the left in wildtype C57/BL6J mice of either sex. No lateralization of GCL volume was found in the androgen-insensitive tfm-affected males or the partially androgen-insensitive tfm-carrier females. These findings confirm earlier reports that sexual dimorphism in mouse HF is found in some inbred strains but not others, and indicate for the first time that mouse HF structures are lateralized. The absence of lateralization in partially or wholly androgen-insensitive mice suggests that androgen receptors may play a role in development of laterality in the GCL independently of any sexual dimorphism in this structure.

Sex differences in spatial learning and prefrontal and parietal cortical dendritic morphology in the meadow vole, Microtus pennsylvanicus

The prefrontal and parietal cortex has been implicated in the mediation of spatially related behaviors in male and female laboratory rats. Meadow voles, Microtus pennsylvanicus, are diurnally–crepuscularly active microtine rodents that exhibit a variety of sexually dimorphic spatially associated behaviors in both the laboratory and wild. In the present study we examined both the spatial Morris water maze performance and dendritic architecture and branching of neuronal cells in the prefrontal and parietal cortex of reproductive male and female meadow voles. Males learned the location of the hidden platform in the water task faster than estrous females and on probe trials they spent more time in the previously correct quadrant than females. Dendritic analysis with Golgi–Cox stained sections showed that male voles had significantly more dendritic arborization in the medial prefrontal and parietal cortex than females. These sex differences in both spatial navigation ability and in neural structures related to spatial navigation in meadow voles suggest that the size of neural areas might be shaped by ecological pressures associated with sexually dimorphic spatial behaviors.

Gonadal Hormone Levels and Spatial Learning Performance in the Morris Water Maze in Male and Female Meadow Voles, Microtus pennsylvanicus

The present study examined the relationships between spatial learning and circulating levels of plasma estradiol and testosterone in adult male and female meadow vole, Microtus pennsylvanicus. Meadow voles are induced ovulators and most females that are housed with females or in isolation are in constant diestrus, whereas most females that are housed with males are in constant behavioral estrus. In this study sexually mature, adult male and female meadow voles housed with either females (constant diestrus) or males (constant behavioral estrus) were required to learn the spatial position of a hidden, submerged platform in the Morris water maze. Individual voles were tested using two blocks of four trials twice a day for 3 days for a total of six blocks. Task retention was examined with a probe trial 1 day after the last acquisition trial. Females were divided into two groups based on the median level of plasma estradiol [High Estradiol (15.79 ? 1.20 pg/ml) and Low Estradiol (6.22 ? 2.79 pg/ml) Females]. Males were similarly divided on the basis of median plasma testosterone levels [High (2.53 ? 0.96 ng/ml) and Low Testosterone (0.45 ? 0.08 ng/ml) Males]. High Estradiol females exhibited significantly longer latencies to reach the hidden platform, indicating poorer acquisition, than did either males (P = 0.025) or Low Estradiol females (for Blocks, 2, 3, 4, and 6, P = 0.037). Male superiority in spatial learning performance was evident only when High Estradiol females were compared to males. There were no significant performance differences between High and Low Testosterone males. There were also no group differences in retention, with all voles displaying significant retention of the spatial task. There was, however, a significant correlation between plasma estradiol levels in females and retention, with higher estradiol levels being associated with poorer retention. These results suggest that levels of estradiol in adult female meadow voles are significantly related to spatial learning, with low levels of estradiol being associated with better spatial learning. There was no evidence that levels of testosterone were related to spatial performance in adult male meadow voles. The results suggest that estradiol may have activational effects on spatial learning in the adult meadow vole and that sex differences in spatial learning are evident only when High Estradiol females are compared to adult males.

Developmental changes in spatial learning in the Morris water-maze in young meadow voles, Microtus pennsylvanicus

Spatial learning in pre- and postweaning meadow voles, ( Microtus pennsylvanicus) was examined in a Morris water-maze task. The learning performance of 10-day-old (preweaning) and 15-, 20- and 25-day-old (postweaning) male and female voles was assessed by measuring the latency to reach a hidden platform by each animal twice a day for 5 days. Voles of all age groups were able to learn the spatial task with Day 10 and Day 15 voles acquiring the task more slowly than did Day 20 and Day 25 voles. There were no significant sex differences in task acquisition in any of the four age groups. In addition, although swimming speed was related to age, with older animals swimming faster than younger ones, differences in swim speed did not account for the faster acquisition by the older animals. These results show that both preweaning and postweaning voles can successfully learn a spatial task. This is in contrast to preweaning laboratory rats which cannot successfully acquire a similar spatial task. These findings indicate that there are species differences in the ontogeny of spatial learning, which are likely related to the ecological and behavioural developmental characteristics of the species. Furthermore, in contrast to the sex difference in water-maze performance obtained in adult, breeding meadow voles who demonstrate a sex difference, there were no significant sex differences in the spatial performance of the juvenile voles. This suggests that sex differences in spatial learning in the meadow vole do not appear until voles reach reproductive adulthood.

Sexual selection for spatial-learning ability

Sex differences in spatial learning have been thought to be universal among mammals, but their adaptive significance has been neglected. Spatial-learning skills are hypothesized to evolve in proportion to nagivational demands, and it is predicted that sex differences in spatial ability will evolve only in species where range expansion contributes differentially to the reproductive success of males and females. This prediction was tested via field studies of ranging behaviour and laboratory studies of spatial ability in two congeneric rodent species whose mating systems differ. Radiotelemetric studies showed that, in a polygynous species (meadow voles, Microtus pennsylvanicus), males expanded their ranges only during the breeding season and only when they attained full reproductive status. Females showed neither response. This suggests that range expansion was a male reproductive tactic. In contrast, a monogamous congener (prairie voles, M. ochrogaster) showed no sex differences in ranging, regardless of reproductive status. This probably reflects the relative inability of monogamous males and females to benefit from increased exposure to members of the opposite sex. When subsequently tested in a series of seven symmetrical mazes, subjects from the field studies exhibited the predicted sex-by-species patterns of spatial ability: only meadow voles showed consistent male superiority on these spatial tasks.