Sex-specific dendritic morphology of hippocampal pyramidal neurons in the adolescent and young adult rats

CA1 and CA3 pyramidal neurons are the major sources of hippocampal efferents. The structural features of these neurons are presumed to be involved in various normal/abnormal cognitive and emotional outcomes by influencing the pattern of synaptic inputs and neuronal signal processing. Although many studies have described hippocampal structure differences between males and females, these reports mainly focused on gross anatomical features in adult or aged models, and such distinctions on neuronal morphology and dendritic spine density during adolescence, a period of high vulnerability to neurodevelopmental disorders, have received much less attention. In this work, we analyzed dendritic architecture and density of spines in CA1 and CA3 neurons of male and female rats in early adolescence (postnatal day, PND 40) and compared them with those in late adolescence/young adulthood (PND 60). On PND 40, CA1 neurons of male rats showed more Sholl intersections and spine density in apical and basal dendrites compared to those in females. The Sholl intersections in basal dendrites of CA3 neurons were also more in males, whereas the number of apical dendrite intersections was not significantly different between sexes. In male rats, there was a notable decrease in the number of branch and terminal points in the basal dendrite of CA1 neurons of young adults when compared to their sex-matched adolescent rats. On the other hand, CA1 neurons in young adult females also showed more Sholl intersections in apical and basal dendrites compared to adolescent females. Meanwhile, the total cable length, the number of branches, and terminal points of apical dendrites in CA3 neurons also exhibited a significant reduction in young adult male rats compared to their sex-matched adolescents. In young adult rats, both apical and basal dendrites of CA3 neurons in males showed fewer intersections with Sholl circles, but there were no significant differences in dendritic spine density or count estimation between males and females. On the other hand, young adult female rats had more Sholl intersections and dendritic spine count on the basal dendrites of CA3 neurons compared to adolescent females. Although no significant sex- and age-dependent difference in neuronal density was detected in CA1 and CA3 subareas, CA3 pyramidal neurons of both male and female rats showed reduced soma area compared to adolescent rats. Our findings show that the sex differences in the dendritic structure of CA1 and CA3 neurons vary by age and also by the compartments of dendritic arbors. Such variations in the morphology of hippocampal pyramidal neurons may take part as a basis for normal cognitive and affective differences between the sexes, as well as distinct sensitivity to interfering factors and the prevalence of neuropsychological diseases.