There is recent evidence of continuing development throughout adolescence in two neural areas involved in emotion and cognition, the basolateral amygdala (BLN) and the medial prefrontal cortex (mPFC). Previous research from our laboratory has demonstrated a cellular loss in both of these brain regions in rats between postnatal day (P) 35 and 90. This study investigates dendritic changes in pyramidal neurons of the BLN and Layer 5 of the mPFC at P20 (juvenile), 35 (puberty), and 90 (adulthood) in hooded rats of both sexes. Dendritic branching and dendritic spines were quantified in Golgi-Cox impregnated tissue. Between P20 and 35, dendritic length and complexity, as well as the density of dendritic spines, increased in both structures. Between P35 and 90, dendritic spines in the mPFC neurons significantly decreased in both sexes, while a loss of basilar dendrites was only detected in females. In the BLN, there was an increase in the number of branches between P35 and 90 without an increase in the total length of the dendritic tree. BLN spine density also remained stable during this period. These results show that the dendritic tree grows prior to puberty while dendritic remodeling and pruning occurs after puberty in both of these neural areas. This late development may lead to susceptibilities to psychopathologies and addictions that often develop at this time.

Sex differences in the function of the hippocampus have been observed in numerous mammalian species. However, the magnitude, extent, and specificity of these differences are unclear because they can depend on factors including age, methodology, and environment. This Review will discuss seminal studies examining sex differences in hippocampal memory, neuronal morphology, synaptic plasticity, and cell signaling in humans and rodents. We also describe possible organizational and activational effects of sex steroid hormones during early development, puberty, and adulthood that may lead to sex differences observed in the hippocampus. We conclude by discussing the implications of sex differences in hippocampal function for mental health. V C 2016 Wiley Periodicals, Inc.Key words: hippocampus; memory; puberty; adolescence; dendritic spines; plasticity; cell signaling Few scientific topics have garnered as much recent attention in both popular and scientific culture as sex differences. Books from the popular press and media reports about new scientific findings or gender inequalities in the workplace have sparked a national conversation about the extent to which men and women differ and whether these differences matter for education, employment, and opportunity. In the wake of high-profile cases in which men and women exhibited different reactions to drugs prescribed to relieve sleep disturbances, allergy symptoms, and gastrointestinal distress (Rabin, 2013), the National Institutes of Health (NIH) has dramatically altered its guidelines for grant proposals, now requiring investigators to consider "sex as a biological variable" in their applications (Clayton, 2016). This new dictum for scientists is a long-overdue response to the fact that very few biomedical research studies have historically included female subjects, and even fewer have directly compared effects between males and females. As stated by the NIH's Office of Women's Health, the policy is designed to "expand our currently incomplete knowledge base that plays a critical role in informing the development of sex-and gender-appropriate medical care for women and men" (Clayton, 2016). We applaud the effort driving this policy and recognize that a key element necessary for its success is a more widespread dissemination of information to biomedical scientists about sex differences, or lack thereof, in the brain and behavior. As such, special issues such as this one and others (McCarthy, 2016) should greatly aid in providing a scientific foundation for investigators new to sex-differences research.Sex differences in cognitive function among humans and nonhuman animals have been reported in earnest for well over 2 decades (Williams et al

The human prefrontal cortex, important for executive functions, loses gray matter throughout the adolescent period. In rats, our laboratory demonstrated that a loss of neurons between adolescence and adulthood partially underlies the loss of volume, and this loss is greater in females than males. Here, we examine whether being deprived of gonadal hormones before puberty through adulthood influences the number of neurons in the medial prefrontal cortex (mPFC). Prior to puberty, the testes or ovaries were removed in male and female rats. In adulthood, the number of neurons and glia in the mPFC were quantified using unbiased stereology, and the volume of the frontal white matter was measured. Prepubertal ovariectomy resulted in a higher number of neurons and glia and a larger volume of white matter compared to sham control littermates. Castrated males were not different from sham males on any measure. Thus ovarian hormones secreted after puberty influence the cellular composition of the medial prefrontal cortex.

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Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol s aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0 g/kg ethanol in a binge-like pattern during postnatal days (PD) 35–45. In adulthood (> PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5 g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females.