The relationship between gonadal hormones and hippocampal neuroplasticity remains controversial. This thesis explores the effects of estradiol on dendritic spine density (DSD) in CA1 and CA3 of the hippocampus in intact female rats. Results showed a mixed-mode response to higher estradiol: CA1 DSD significantly increased in the apical dendritic tree, but not in CA3. Despite evidence that CA3 synaptic characteristics are dependent on BDNF and estradiol interactions, other mechanisms maybe involved. This thesis also addresses the connection between androgen and BDNF-dependent mechanisms on hippocampal neuroplasticity in male mice. Gonadectomy led to atrophy of CA3 neurons but did not alter BDNF transcript or protein expression. Interestingly, surgerized groups expressed greater proBDNF 8-12 days, not 27-30 days following surgery, and atrophy in CA3 neurons compared to un-surgerized groups. It is likely that surgical stress might have played a role in the neuromorphological changes observed. This is key to understanding hippocampal- dependent cognitive dysfunction.