A test of the social behavior network reveals differential patterns of neural responses to social novelty in bonded, but not non-bonded, male prairie voles.

The social behavior network (SBN) has provided a framework for understanding the neural control of social behavior. The original SBN hypothesis proposed this network modulates social behavior and should exhibit distinct patterns of neural activity across nodes, which correspond to distinct social contexts. Despite its tremendous impact on the field of social neuroscience, no study has directly tested this hypothesis. Thus, we assessed Fos responses across the SBN of male prairie voles (Microtus ochrogaster). Virgin/non-bonded and pair bonded subjects were exposed to a sibling cagemate or pair bonded partner, novel female, novel male, novel meadow vole, novel object, or no stimulus. Inconsistent with the original SBN hypothesis, we did not find profoundly different patterns of neural responses across the SBN for different contexts, but instead found that the SBN generated significantly different patterns of activity in response to social novelty in pair bonded, but not non-bonded males. These findings suggest that non-bonded male prairie voles may perceive social novelty differently from pair bonded males or that SBN functionality undergoes substantial changes after pair bonding. This study reveals novel information about bond-dependent, context-specific neural responsivity in male prairie voles and suggests that the SBN may be particularly important for processing social salience. Further, our study suggests there is a need to reconceptualize the framework of how the SBN modulates social behavior.

Behavioral, neurochemical, and neuroimmune changes associated with social buffering and stress contagion.

Social buffering can provide protective effects on stress responses and their subsequent negative health outcomes. Although social buffering is beneficial for the recipient, it can also have anxiogenic effects on the provider of the social buffering - a phenomena referred to as stress contagion. Social buffering and stress contagion usually occur together, but they have traditionally been studied independently, thus limiting our understanding of this dyadic social interaction. In the present study, we examined the effects of preventative social buffering and stress contagion in socially monogamous prairie voles (Microtus ochrogaster). We tested the hypothesis that this dynamic social interaction is associated with coordinated alterations in behaviors, neurochemical activation, and neuroimmune responses. To do so, adult male prairie voles were stressed via an acute immobilization restraint tube (IMO) either alone (Alone) or with their previously pair-bonded female partner (Partner) in the cage for 1 h. In contrast, females were placed in a cage containing either an empty IMO tube (Empty) or one that contained their pair-bonded male (Partner). Anxiety-like behavior was tested on the elevated plus maze (EPM) following the 60-mins test and brain sections were processed for neurochemical/neuroimmune marker labeling for all subjects. Our data indicate that females in the Partner group were in contact with and sniffed the IMO tube more, showed fewer anxiety-like behaviors, and had a higher level of oxytocin expression in the paraventricular nucleus of the hypothalamus (PVN) compared to the Empty group females. Males in the Partner group had lower levels of anxiety-like behavior during the EPM test, greater activation of corticotropin-releasing hormone expressing neurons in the PVN, lower activation of serotonin neurons in the dorsal raphe, and lower levels of microgliosis in the nucleus accumbens. Taken together, these data suggest brain region- and neurochemical-specific alterations as well as neuroinflammatory changes that may be involved in the regulation of social buffering and stress contagion behaviors.

Post-weaning Social Isolation in Male and Female Prairie Voles: Impacts on Central and Peripheral Immune System.

The socially monogamous prairie vole (Microtus ochrogaster) offers a unique opportunity to examine the impacts of adolescent social isolation on the brain, immune system, and behavior. In the current study, male and female prairie voles were randomly assigned to be housed alone or with a same-sex cagemate after weaning (i.e., on postnatal day 21-22) for a 6-week period. Thereafter, subjects were tested for anxiety-like and depressive-like behaviors using the elevated plus maze (EPM) and Forced Swim Test (FST), respectively. Blood was collected to measure peripheral cytokine levels, and brain tissue was processed for microglial density in various brain regions, including the Nucleus Accumbens (NAcc), Medial Amygdala (MeA), Central Amygdala (CeA), Bed Nucleus of the Stria Terminalis (BNST), and Paraventricular Nucleus of the Hypothalamus (PVN). Sex differences were found in EPM and FST behaviors, where male voles had significantly lower total arm entries in the EPM as well as lower latency to immobility in the FST compared to females. A sex by treatment effect was found in peripheral IL-1ß levels, where isolated males had a lower level of IL-1ß compared to cohoused females. Post-weaning social isolation also altered microglial density in a brain region-specific manner. Isolated voles had higher microglial density in the NAcc, MeA, and CeA, but lower microglial density in the dorsal BNST. Cohoused male voles also had higher microglial density in the PVN compared to cohoused females. Taken together, these data suggest that post-weaning social housing environments can alter peripheral and central immune systems in prairie voles, highlighting a potential role for the immune system in shaping isolation-induced alterations to the brain and behavior.