Examining the contributions of desirable difficulty and reminding to the spacing effect.

Although substantial evidence indicates that spacing repeated study events with intervening material generally enhances memory performance relative to massing study events, the mechanism underlying this benefit is less clear. Two experiments examined the role of reminding difficulty during the acquisition of material in modulating final memory performance for spaced repetitions utilizing recognition (Experiment 1) and recall tests (Experiment 2). Specifically, participants studied a list of words presented one or two times separated by one or five items. On each trial participants reported whether the item had been previously presented (i.e., repetition detection judgment), and the response latency served as a proxy for reminding difficulty such that longer response latencies reflected more difficult reminding. A third experiment extended this paradigm with the inclusion of a massed condition and novel lag conditions (three and ten items). Results revealed significant lag effects in final test performance across experiments despite comparable repetition detection difficulty between lag conditions during acquisition. Moreover, results from within-participant point-biserial analyses and mediation analyses converged on overall performance measures in suggesting that repetition detection difficulty failed to modulate final test performance in the current paradigm. Discussion considers the implications of the current results for mechanisms proposed to underlie the benefits of spaced study and spaced retrieval practice.

Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression.

Bisphenol A (BPA) is a plasticizer and an endocrine-disrupting chemical. It is present in a variety of products used daily including food containers, paper, and dental sealants and is now widely detected in human urine and blood. Exposure to BPA during development may affect brain organization and behavior, perhaps as a consequence of its actions as a steroid hormone agonist/antagonist and/or an epigenetic modifier. Here we show that BPA produces transgenerational alterations in genes and behavior. Female mice received phytoestrogen-free chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented dams were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice, whereas in later generations (F(2) and F(4)), the effect of BPA was to increase these social interactions. Brains from embryos (embryonic d 18.5) exposed to BPA had lower gene transcript levels for several estrogen receptors, oxytocin, and vasopressin as compared with controls; decreased vasopressin mRNA persisted into the F(4) generation, at which time oxytocin was also reduced but only in males. Thus, exposure to a low dose of BPA, only during gestation, has immediate and long-lasting, transgenerational effects on mRNA in brain and social behaviors. Heritable effects of an endocrine-disrupting chemical have implications for complex neurological diseases and highlight the importance of considering gene-environment interactions in the etiology of complex disease.

Gestational exposure to bisphenol A and cross-fostering affect behaviors in juvenile mice.

Bisphenol-A (BPA) is a component of polycarbonate resins, and, lately, concern has been raised about its potential negative effects on human health. BPA is an estrogen analog and, in addition, it can act as a DNA hypomethylator. We examined the effects of gestational exposure to BPA on several behaviors in C57BL/6J mice. Because BPA affects maternal care, which, may have long-lasting effects on offspring behavior, we tested mice raised by either biological or fostered dams. Both diet and dam affected behavior in juvenile mice in a social novelty task and the elevated plus maze (EPM). In a social novelty task, the amount of time spent interacting with an adult male was affected by sex and gestational diet, but only in juveniles raised by a foster dam. Control females spent less time sniffing a novel adult than did control males or females exposed to BPA during gestation. In the EPM, juveniles reared by foster dams and exposed to BPA during gestation spent less time in the distal half of the open arm as compared with juveniles gestated on a control diet. Adult offspring raised by their biological dams showed the same response pattern; gestational BPA increased anxiety as compared with control diet. Our results show that prenatal BPA exposure affects social behavior and anxiety in the EPM. Moreover, some facet(s) of the infant-maternal interaction may modify these effects.

Sex chromosome complement and gonadal sex influence aggressive and parental behaviors in mice.

Across human cultures and mammalian species, sex differences can be found in the expression of aggression and parental nurturing behaviors: males are typically more aggressive and less parental than females. These sex differences are primarily attributed to steroid hormone differences during development and/or adulthood, especially the higher levels of androgens experienced by males, which are caused ultimately by the presence of the testis-determining gene Sry on the Y chromosome. The potential for sex differences arising from the different complements of sex-linked genes in male and female cells has received little research attention. To directly test the hypothesis that social behaviors are influenced by differences in sex chromosome complement other than Sry, we used a transgenic mouse model in which gonadal sex and sex chromosome complement are uncoupled. We find that latency to exhibit aggression and one form of parental behavior, pup retrieval, can be influenced by both gonadal sex and sex chromosome complement. For both behaviors, females but not males with XX sex chromosomes differ from XY. We also measured vasopressin immunoreactivity in the lateral septum, which was higher in gonadal males than females, but also differed according to sex chromosome complement. These results imply that a gene(s) on the sex chromosomes (other than Sry) affects sex differences in brain and behavior. Identifying the specific X and/or Y genes involved will increase our understanding of normal and abnormal aggression and parental behavior, including behavioral abnormalities associated with mental illness.

Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat.

The current work examined spatial learning and memory (i.e., latencies to find a baited food well) in age-matched nulliparous, primiparous and multiparous (NULL, PRIM and MULT, zero, one or two pregnancies and lactations, respectively). We tested at 6, 12, 18 and 24 months of age in a dry land version of the Morris water maze (Main task), and at 12, 18 and 24 months in the same task in which the original location of the baited well was changed (Reversal task). We show that PRIM/MULT rats, compared to the age-matched NULL females, learned the spatial tasks significantly better and exhibited attenuated memory decline, up to 24 months of age. Furthermore, at the conclusion of behavioral testing, we investigated levels of these animals' hippocampal (CA1 and dentate gyrus) immunoreactive amyloid precursor protein (APP), a marker of neurodegeneration and age-related cognitive loss. MULTs had significantly reduced APP in both CA1 and DG, relative to PRIMs and NULLs, and PRIMs had a trend (p<0.06) toward a reduction in APP compared to NULLs in DG. Further, level of APP was negatively correlated with performance in the two tasks (viz., more APP, worse maze performance). Reproduction, therefore, with its attendant natural endocrine and postpartum sensory experiences, may facilitate lifelong learning and memory, and may mitigate markers of neural aging, in the rat. Combining natural hormonal exposure with subsequent substantial experience with stimuli from the offspring may preserve the aged parous female brain relative to that of NULL females.