Project Summary
Social stress is a risk factor for several stress-related psychopathologies, including post-traumatic
stress disorder (PTSD). However, most individuals exposed to trauma do not develop stress-related
psychopathologies and previous social experience has the potential to improve coping strategies and enable
stress resilience. One social experience that contributes to the development of stress resilience is a dominant
position in a social hierarchy. In this proposal, we use a Syrian hamster model in which dominant animals show
less stress-related behavior than their subordinate counterparts. Our preliminary data indicate that male
dominants show increased c-Fos immunoreactivity in androgen receptor (AR)-positive cells in dorsal aspects
of the posterior medial amygdala (MePD) compared to their subordinate counterparts. In addition, they show
increased c-Fos immunoreactivity in MePD cells projecting to posterior regions of the bed nucleus of the stria
terminalis (BNSTp) compared to subordinates. Unlike males, dominant female hamsters have a greater
number of estrogen receptor alpha (ERa)-positive cells in the MePD compared to subordinates. However,
dominant females do not show elevated c-Fos immunoreactivity in BNSTp-projecting MePD cells compared to
subordinates. Altogether, these findings suggest that while AR expression in a MePD-BNSTp pathway may be
critical for status-dependent differences in stress vulnerability in male hamsters, ERa expression in MePD-
BNSTp pathway may not contribute to status-dependent differences in stress vulnerability in female hamsters.
Because of these sex differences, we have two separate hypotheses in this proposal. We hypothesize that
AR+ neurons in a MePD-BNSTp pathway are essential for status-dependent differences in stress-related
behavior in male hamsters. Also, we hypothesize that ERa+ cells in the MePD are necessary for status-
dependent differences in stress-related behavior in female hamsters. We will use a Cre-dependent AAV vector
that expresses a short hairpin RNA (shRNA) for AR to selectively knockdown AR receptors in a MePD-BNSTp
pathway. In addition, we will use an AAV-shRNA to knockdown ERa receptors in the MePD in a non-Cre-
dependent manner in both females and males. Overall, this project will investigate the cellular mechanisms
and neural circuits by which gonadal steroid hormone receptors contribute to status-dependent changes in
stress vulnerability. This line of research will determine how social experience generates neural plasticity in
select neural ensembles and thereby changes stress vulnerability in a sex-dependent manner.