Neuro- and gliogenesis in the pubertal rat brain: Implications for female reproduction

Puberty and adolescence are associated with a gain of function in brain circuits that regulate sex-specific physiology and behavior. One of the most striking sex differences to arise during puberty in rats is the capacity to generate a surge of luteinizing hormone (LH), which females, but not males, produce as part of ovarian cyclicity. The preovulatory LH surge is controlled by the anteroventral periventricular nucleus of the hypothalamus (AVPV). The AVPV is sexually dimorphic in structure; in females the AVPV is larger and contains more neurons compared to males. Previous work in my advisor and co-advisor's laboratory has demonstrated sex differences in the addition of new cells, including both neurons and glia, to the AVPV during puberty. Gonadal hormones drive these particular sex differences, as they are abolished by prepubertal gonadectomy. A key question is whether these newly added cells contribute to the sex-specific regulation of physiology and behavior that arises during puberty. Because the LH surge cannot be elicited before puberty in female rats, perhaps the cellular machinery responsible for regulation of the LH surge and ovarian cyclicity is not yet in place. The goal of the experiments conducted in this dissertation was to test the hypothesis that cells added to the AVPV during puberty are functionally incorporated into the neural circuitry involved in female-specific regulation of the hypothalamic-pituitary-gonadal (HPG) axis that controls the LH surge and ovarian cyclicity. The first aim replicated a sex difference previously seen in the addition of cells to the AVPV during puberty and determined that this sex difference was due to greater cell addition in female rats compared to males. Furthermore, it employed immunofluorescent labeling to determine that pubertally born cells in the AVPV include neurons, astrocytes, and microglia. The second aim determined that pubertally and adult-born cells are active at the time of the LH surge, and that knockdown of either pubertally or adult-born cells attenuated and delayed the LH surge. These studies further our understanding of the function of pubertally added cells to sexually dimorphic brain regions, and have provided insight into how sex-specific regulation of the HPG axis is established during puberty and maintained in adulthood.