Increased Testosterone Decreases Medial Cortical Volume and Neurogenesis in Territorial Side-Blotched Lizards (Uta stansburiana)

Lara D. LaDage, Timothy C. Roth, Cynthia J. Downs, Barry Sinervo, Vladimir V. Pravosudov

Variation in an animal's spatial environment can induce variation in the hippocampus, an area of the brain involved in spatial cognitive processing. Specifically, increased spatial area use is correlated with increased hippocampal attributes, such as volume and neurogenesis. In the side-blotched lizard (Uta stansburiana), males demonstrate alternative reproductive tactics and are either territorial-defending large, clearly defined spatial boundaries-or non-territorial-traversing home ranges that are smaller than the territorial males' territories. Our previous work demonstrated cortical volume (reptilian hippocampal homolog) correlates with these spatial niches. We found that territorial holders have larger medial cortices than non-territory holders, yet these differences in the neural architecture demonstrated some degree of plasticity as well. Although we have demonstrated a link among territoriality, spatial use, and brain plasticity, the mechanisms that underlie this relationship are unclear. Previous studies found that higher testosterone levels can induce increased use of the spatial area and can cause an upregulation in hippocampal attributes. Thus, testosterone may be the mechanistic link between spatial area use and the brain. What remains unclear, however, is if testosterone can affect the cortices independent of spatial experiences and whether testosterone differentially interacts with territorial status to produce the resultant cortical phenotype. In this study, we compared neurogenesis as measured by the total number of doublecortin-positive cells and cortical volume between territorial and non-territorial males supplemented with testosterone. We found no significant differences in the number of doublecortin-positive cells or cortical volume among control territorial, control non-territorial, and testosterone-supplemented non-territorial males, while testosterone-supplemented territorial males had smaller medial cortices containing fewer doublecortin-positive cells. These results demonstrate that testosterone can modulate medial cortical attributes outside of differential spatial processing experiences but that territorial males appear to be more sensitive to alterations in testosterone levels compared with non-territorial males.