Socially Modulated Cell Proliferation Is Independent of Gonadal Steroid Hormones in the Brain of the Adult Green Treefrog <i>(Hyla cinerea)</i>

Abstract

Gonadal steroid hormones have been shown to influence adult neurogenesis in addition to their well-defined role in regulating social behavior. Adult neurogenesis consists of several processes including cell proliferation, which can be studied via 5-bromo-2′-deoxyuridine (BrdU) labeling. In a previous study we found that social stimulation altered both cell proliferation and levels of circulating gonadal steroids, leaving the issue of cause/effect unclear. In this study, we sought to determine whether socially modulated BrdU-labeling depends on gonadal hormone changes. We investigated this using a gonadectomy-implant paradigm and by exposing male and female green treefrogs (Hyla cinerea) to their conspecific chorus or control stimuli (i.e. random tones). Our results indicate that socially modulated cell proliferation occurred independently of gonadal hormone levels; furthermore, neither androgens in males nor estrogen in females increased cell proliferation in the preoptic area (POA) and infundibular hypothalamus, brain regions involved in endocrine regulation and acoustic communication. In fact, elevated estrogen levels decreased cell proliferation in those brain regions in the implanted female. In male frogs, evoked calling behavior was positively correlated with BrdU-labeling in the POA; however, statistical analysis showed that this behavior did not mediate socially induced cell proliferation. These results show that the social modulation of cell proliferation can occur without gonadal hormone involvement in either male or female adult anuran amphibians, and confirms that it is independent of a behavioral response in males.

Cellular profiling of a recently-evolved social behavior

“…Together our data suggest that programs underlying cell type-specific neurogenesis may have been integral to the evolution of castle-building behavior, and may also be important for its active expression. More broadly, these results fit with a large body of work showing changes in brain region-specific neurogenesis in other social and reproductive contexts across species (Walton, Pariser, and Nottebohm 2012; Bedos, Portillo, and Paredes 2018; Almli and Wilczynski 2012; Balthazart and Ball 2016; Maruska, Carpenter, and Fernald 2012; Dunlap, Chung, and Castellano 2013; Lévy et al 2017).…”

Seasonal Variation in Cell Proliferation and Cell Migration in the Brain of Adult Red-Sided Garter Snakes <b><i>(Thamnophis sirtalis parietalis)</i></b>

“…Rasika et al [1994] demonstrated that androgens affect cell recruitment and survival, but not cell proliferation, in Waterslager canaries. In contrast, social modulation of cell proliferation in the brain of green treefrogs (H. cinerea) is independent of sex steroid hormone concentrations in both males and females, and sex steroids do not directly influence cell proliferation alone [Almli and Wilczynski, 2012]. Similar findings that sex steroid hormones are not the primary factor regulating cell proliferation in the brain have been reported in canaries ( Serinus canaria) [Brown et al, 1993] and weakly electric fish ( Brachyhypopomus gauderio ) [Dunlap et al 2011].…”

Plasticity and Adult Neurogenesis in Amphibians and Reptiles: More Questions than Answers

“…These results were partially replicated in a second study [Almli and Wilczynski, 2012], but in that study there was also a significant effect of conspecific calls on the infundibular hypothalamus of males. Thus, social stimulation increases new cell production in the hypothalamus of these frogs.…”

“…Removal of testosterone via castration did not significantly alter the production of new cells in the hypothalamus in response to conspecific calls in green tree frogs (H. cinerea) [Almli and Wilczynski, 2012]. In their earlier study [Almli and Wilczynski, 2009], in contrast, these investigators found a significant positive correlation between testosterone levels and BrdU-positive cells in the preoptic area but not in the infundibular area in males.…”