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

Abstract

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.

Sexually Dimorphic Patterns of Cell Proliferation in the Brain Are Linked to Seasonal Life-History Transitions in Red-Sided Garter Snakes

“…The processes that characterize neurogenesis are subject to hormonal regulation, and therefore the influence of sex steroid hormones (or other sexually dimorphic endocrine factors, including glucocorticoid “stress” hormones) on cell proliferation and migration may contribute to the sex differences reported here (see reviews in Balthazart and Ball, 2016 ; Dunlap, 2016 ; Mahmoud et al, 2016 ; Powers, 2016 ). For example, treatment of territorial, but not non-territorial male side-blotched lizards ( Uta stansburiana ) with testosterone decreased the volume of the medial cortex and reduced the number of doublecortin-positive cells, an indicator of immature, migrating neurons (LaDage et al, 2017 ). Pellegrini et al ( 2007 ) showed that radial glial cells in the zebrafish forebrain express aromatase, the enzyme that synthesizes estrogens from androgens.…”

Radial stem astrocytes (aka neural stem cells): Identity, development, physio‐pathology, and therapeutic potential

“…Rodent‐centric views and associated bias are frequently questioned 3 . Adult neurogensis and RSA were characterised in fishes, reptiles, birds, and the majority of wild mammals 120‐125 . Thus adult neurogenesis seems to be evolutionarily conserved, driven by the needs of environmental adaptations.…”

“…3 Adult neurogensis and RSA were characterised in fishes, reptiles, birds, and the majority of wild mammals. [120][121][122][123][124][125] Thus adult neurogenesis seems to be evolutionarily conserved, driven by the needs of environmental adaptations. The details of adult neurogenesis in humans (especially in the hippocampus), however, remain to be elucidated.…”

Higher Rate of Male Sexual Displays Correlates with Larger Ventral Posterior Amygdala Volume and Neuron Soma Volume in Wild-Caught Common Side-Blotched Lizards, <b><i>Uta stansburiana</i></b>

“…Following previous methods in this species [LaDage et al, 2009[LaDage et al, , 2013[LaDage et al, , 2017, brains were sectioned on a cryostat (Leica CM 3050S, -20°C) in the coronal plane every 50 μm, and every other section was mounted and Nissl-stained with thionin to visualize the brain region boundaries (Fig. 2a) and the VPA neuron somas (Fig.…”

“…Specifically, the VPA (Fig. 2a) and remainder of the telencephalon (i.e., total telencephalon volume minus VPA volume) were outlined around their boundaries (contoured) within the software to assess if any population effects were specific to the VPA or representative of global changes within the brain [LaDage et al, 2009[LaDage et al, , 2013[LaDage et al, , 2017. We contoured both the left and right hemispheres to account for lateralization, as some previous studies have demonstrated differential activation between the left and right amygdala in mammals [reviewed in Baas et al, 2004].…”