Dominance status modulates activity in medial amygdala cells with projections to the bed nucleus of the stria terminalis.

The medial amygdala (MeA) controls several types of social behavior via its projections to other limbic regions. Cells in the posterior dorsal and posterior ventral medial amygdala (MePD and MePV, respectively) project to the bed nucleus of the stria terminalis (BNST) and these pathways respond to chemosensory cues and regulate aggressive and defensive behavior. Because the BNST is also essential for the display of stress-induced anxiety, a MePD/MePV-BNST pathway may modulate both aggression and responses to stress. In this study we tested the hypothesis that dominant animals would show greater neural activity than subordinates in BNST-projecting MePD and MePV cells after winning a dominance encounter as well as after losing a social defeat encounter. We created dominance relationships in male and female Syrian hamsters (Mesocricetus auratus), used cholera toxin b (CTB) as a retrograde tracer to label BNST-projecting cells, and collected brains for c-Fos staining in the MePD and MePV. We found that c-Fos immunoreactivity in the MePD and MePV was positively associated with aggression in males, but not in females. Also, dominant males showed a greater proportion of c-Fos+ /CTB+ double-labeled cells compared to their same-sex subordinate counterparts. Another set of animals received social defeat stress after acquiring a dominant or subordinate social status and we stained for stress-induced c-Fos expression in the MePD and MePV. We found that dominant males showed a greater proportion of c-Fos+ /CTB+ double-labeled cells in the MePD after social defeat stress compared to subordinates. Also, dominants showed a longer latency to submit during social defeat than subordinates. Further, in males, latency to submit was positively associated with the proportion of c-Fos+ /CTB+ double-labeled cells in the MePD and MePV. These findings indicate that social dominance increases neural activity in BNST-projecting MePD and MePV cells and activity in this pathway is also associated with proactive responses during social defeat stress. In sum, activity in a MePD/MePV-BNST pathway contributes to status-dependent differences in stress coping responses and may underlie experience-dependent changes in stress resilience.

Sex differences in dominance relationships in Syrian hamsters.

Dominance relationships are identified by changes in agonistic behavior toward specific individuals. While there are considerable individual and species differences in dominance relationships, sex differences are poorly understood in rodent models because aggression among female rodents is rare. The aim of this study was to characterize sex differences in the formation and maintenance of dominance relationships in same-sex pairs of male and female Syrian hamsters. We pooled data from multiple projects in our lab to evaluate dominance interactions in 68 male dyads and 88 female dyads. In each project, animals were matched with a partner similar in age, sex, and estrous cycle and we exposed animals to daily social encounters for two weeks in a resident-intruder format. We found that female hamsters were quicker to attack and attacked at higher rates compared to males regardless of dominance status. In addition, resident female hamsters were quicker to attack and attacked at higher rates than intruder females, but aggression in males did not depend on residency status. Female subordinates were quicker to submit and fled at higher rates from their dominant counterparts compared to male subordinates. Intruder subordinate females were quicker to submit and fled at higher rates than resident subordinate females. Females were also more resistant than males to becoming subordinate in that they fought back more consistently and were more likely to reverse their dominance status. These findings indicate that dominance relationships are less stable in females compared to males and that residency status has a larger impact on agonistic behavior in females than males. Overall, differences in how males and females display territorial aggression can lead to sex differences in the establishment and maintenance of dominance relationships.

Comparing the ontogeny, neurobiology, and function of social play in hamsters and rats.

Syrian hamsters show complex social play behavior and provide a valuable animal model for delineating the neurobiological mechanisms and functions of social play. In this review, we compare social play behavior of hamsters and rats and underlying neurobiological mechanisms. Juvenile rats play by competing for opportunities to pin one another and attack their partner's neck. A broad set of cortical, limbic, and striatal regions regulate the display of social play in rats. In hamsters, social play is characterized by attacks to the head in early puberty, which gradually transitions to the flanks in late puberty. The transition from juvenile social play to adult hamster aggression corresponds with engagement of neural ensembles controlling aggression. Play deprivation in rats and hamsters alters dendritic morphology in mPFC neurons and impairs flexible, context-dependent behavior in adulthood, which suggests these animals may have converged on a similar function for social play. Overall, dissecting the neurobiology of social play in hamsters and rats can provide a valuable comparative approach for evaluating the function of social play.

Chemogenetic activation of an infralimbic cortex to basolateral amygdala projection promotes resistance to acute social defeat stress.

Tremendous individual differences exist in stress responsivity and social defeat stress is a key approach for identifying cellular mechanisms of stress susceptibility and resilience. Syrian hamsters show reliable territorial aggression, but after social defeat they exhibit a conditioned defeat (CD) response characterized by increased submission and an absence of aggression in future social interactions. Hamsters that achieve social dominance prior to social defeat exhibit greater defeat-induced neural activity in infralimbic (IL) cortex neurons that project to the basolateral amygdala (BLA) and reduced CD response compared to subordinate hamsters. Here, we hypothesize that chemogenetic activation of an IL-to-BLA neural projection during acute social defeat will reduce the CD response in subordinate hamsters and thereby produce dominant-like behavior. We confirmed that clozapine-N-oxide (CNO) itself did not alter the CD response and validated a dual-virus, Cre-dependent, chemogenetic approach by showing that CNO treatment increased c-Fos expression in the IL and decreased it in the BLA. We found that CNO treatment during social defeat reduced the acquisition of CD in subordinate, but not dominant, hamsters. This project extends our understanding of the neural circuits underlying resistance to acute social stress, which is an important step toward delineating circuit-based approaches for the treatment of stress-related psychopathologies.