Elsevier

Brain Research

Volume 1460, 15 June 2012, Pages 33-40
Brain Research

Research Report
Pubertal testosterone organizes regional volume and neuronal number within the medial amygdala of adult male Syrian hamsters

https://doi.org/10.1016/j.brainres.2012.04.035Get rights and content

Abstract

The medial amygdala plays a key role in regulating adult social behavior and undergoes structural changes during puberty that may be driven by gonadal hormone secretion during this developmental period. The current study sought to investigate potential organizational effects of testosterone during puberty, activational effects of testosterone in adulthood, and any interactions on regional volume and neuronal number of the medial amygdala. Male Syrian hamsters either did or did not experience endogenous testosterone during pubertal brain development, and then received either testosterone-filled or blank capsules during adulthood 2 weeks before tissue collection. The results show that pubertal testosterone has long-term organizational effects on volume of specific subregions of the medial amygdala such that the presence of pubertal testosterone resulted in 1) decreased volume of the anterior ventral amygdala and, to a lesser extent, the anterior dorsal medial amygdala; and 2) increased volume of the posterior dorsal medial amygdala. Both effects were independent of the presence of testosterone during adulthood. Pubertal testosterone also decreased neuronal number in the anterior dorsal medial amygdala, suggesting a possible mechanism by which pubertal testosterone decreases volume in this subregion. In addition, there was a significant interaction between pubertal and adult testosterone, such that testosterone in adulthood increased the number of neurons in the posterior ventral medial amygdala only in males that did not experience endogenous pubertal testosterone. In conclusion, pubertal testosterone organizes the medial amygdala in a subregion-specific manner, which may contribute to the maturation of adult-typical social behavior.

Highlights

► Pubertal testosterone organizes the medial amygdala in a subregion-specific manner. ► Adult testosterone had no effect on medial amygdala volume or neuron number. ► Neuronal number contributes to volume changes in a subregion-specific manner. ► Volume and neuronal number are independently affected by pubertal testosterone.

Introduction

Many of the physiological and behavioral changes associated with adolescence can be attributed to puberty and the associated increase in gonadal steroid hormones. These hormones influence the adolescent brain and maturation of social behaviors necessary for survival and reproduction in adulthood. Gonadal hormones have two modes of action on social behaviors and their underlying neural circuits: long-lasting organizational influences that typically occur during development, and short-term activational influences that typically occur in adulthood. Activational responses to hormones are often programmed by earlier organizational effects. For example, the perinatal organization of the brain by testicular hormones sets up male-typical behavioral responses to testosterone in adulthood (for a review, see Arnold, 2009).

Using the male Syrian hamster as an animal model to understand neuroendocrine mechanisms underlying the maturation of adult social behaviors, we have shown that puberty is an extension of the perinatal period of sensitivity to organizing effects of testicular hormones (Schulz and Sisk, 2006, Schulz et al., 2004, Schulz et al., 2009). Depriving males of testosterone during puberty results in long-lasting deficits in hormone-dependent reproductive and agonistic behavior. Thus, it appears that pubertal testosterone organizes the male brain a second time, perhaps by fine-tuning the perception of socially relevant sensory stimuli (Romeo et al., 2003, Schulz et al., 2004, Schulz et al., 2006, Schulz et al., 2009). In the current study we sought to determine whether there are organizational influences of pubertal testosterone on gross morphological features of the medial amygdala (Me) in light of its key role in the expression of adult social behaviors, namely, the integration of chemosensory social cues with the internal steroid hormone milieu (Choi et al., 2005, Wood, 1998).

The rodent Me is subdivided into four well-defined subregions, or quadrants, based on differing cytoarchitecture, connectivity, steroid hormone receptor expression, and function: anterior ventral (MeAV), anterior dorsal (MeAD), posterior ventral (MePV), and posterior dorsal (MePD) (for a review, see Petrulis, 2009). Region-specific structural changes occur in all quadrants during pubertal development, including alterations in volume, cell number, and dendritic morphology (Ahmed et al., 2008, Cooke et al., 2007, Romeo and Sisk, 2001, Schulz et al., 2009, Zehr et al., 2006). For example, in Syrian hamsters, MeAD volume decreases, whereas MePD volume increases, across pubertal development (Romeo and Sisk, 2001, Schulz et al., 2009). It is not clear whether these developmental changes in volume are the result of organizational or activational effects of testicular hormones, or neither. However, generally speaking, Me volume is subject to activational influences of testosterone in adulthood, since castration in adulthood typically reduces volume, and testosterone replacement restores it to pre-castration size (Cooke et al., 1999, Cooke et al., 2002, Cooke et al., 2003, Morris et al., 2008a, Morris et al., 2008b). Furthermore, activational influences of testosterone on Me volume in adulthood may be programmed by organizational influences of testosterone during puberty.

The current study was designed to tease apart organizational and activational influences of testosterone, and any interactions, on gross morphology of Me. We used a 2 by 2 design in which male Syrian hamsters either did or did not experience endogenous circulating testosterone during adolescence (gonadectomy either prepubertally or in adulthood), and either did or did not receive exogenous testosterone replacement in adulthood 6 weeks after gonadectomy. We focused on regional volume and neuronal number as easily quantified structural features by which to compare potential organizational and activational effects of testosterone across the Me quadrants. This study identified organizational influences of pubertal testosterone on Me regional volume and neuron number that are structural correlates of the organizational influences of pubertal testosterone on male social behaviors.

Section snippets

Testosterone concentrations within each experimental group

Adult males given testosterone-filled capsules (T-treated) that went through pubertal development either without (NoT@P) or with (T@P) endogenous testosterone had circulating testosterone concentrations within adult male physiological range (3.00 ± 0.55 ng/mL and 3.61 ± 0.41 ng/mL, respectively). As expected, NoT@P and T@P males given blank capsules (blank-treated) had nearly undetectable levels of circulating testosterone (0.12 ± 0.05 ng/mL and 0.11 ± 0.07 ng/mL, respectively).

Effects of pubertal and adult testosterone on Me regional volume

Two-way ANOVA revealed a

Discussion

This is the first documentation of organizational effects of pubertal testosterone on regional volume and neuronal number within the male Syrian hamster Me. The presence of pubertal testosterone resulted in decreased volume or neuronal number in the anterior Me subregions, independently of the presence or absence of testosterone in adulthood. In contrast, the presence of testosterone during puberty resulted in increased regional volume of MePD. It is unlikely that the decrease in anterior Me

Animals

Thirty-two 18 day old (P18) male Syrian hamsters (Mesocricetus auratus) were obtained from Harlan Sprague–Dawley laboratories (Madison, WI) and arrived with their mothers. Males were housed with mothers and littermates until weaning at 21 days of age. Thereafter, they were housed individually in clear polycarbonate cages (12 × 4 × 8 in.) with ad libitum access to food (Telkad Rodent Diet No. 8640, Harlan) and water. Colony rooms were maintained on a 14 h light/10 h dark schedule (lights off at 1200 h

Acknowledgments

This work was supported by National Institutes of Health grants R01-MH068764 to C.L.S. and T32-MH070343 support of K.C.D. Many thanks to Margaret Bell, Margaret Mohr, Ashley Pratt, Dr. Heather Molenda-Figueira, Dr. Eman Ahmed, Dr. Sarah Meerts, Jane Venier, and Rayson Figueira for their contributions to data collection and comments on this manuscript.

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