THE NEUROBIOLOGY OF STRESS AND SOCIAL BONDS

Social bonds are essential for survival and reproduction, particularly in social species such as humans. The driving forces that facilitate social attachments, such as pair bonding, include reinforcing social behaviors through activating the brain reward centers, the consequences of disruption or separation of close social bonds on an individual’s well-being and emotional state, and the beneficial effects of close social contact to improve mental and physical health. Still, many fundamental questions regarding the underlying neurobiology of social bonds remains unanswered. Our research goal is to perform a multi-level analysis across cellular, genetic, systems/circuit, and behavioral levels to outline the neurobiology of social bonds and the impact of social living on individual well-being. 

Neurocircuitry regulating the behavioral and hormonal response to social defeat in males and females

Repeated negative social interactions can have a lasting effect on behavior and neurobiology of an individual. Social conflict in humans (e.g., bullying, domestic violence, and violent crimes) represents significant negative social events reported by individuals with social anxiety disorder at the etiology of this condition, which affects 7% of U.S. adults annually. Ethologically-relevant animal models that examine social conflict, such as social defeat (repeated exposure to overt aggression and physical dominance), have been particularly useful for determining how social experience alters the brain and behavior. Currently, most defeat models use rodent species that restrict research to male-male aggression, limiting any potential focus on the consequences of conflict in females or sex differences. Our research group has developed a novel animal model of social defeat which allows us to study the neurobiology of social anxiety behaviors in both males and females. Specifically, our model focuses on the socially monogamous prairie vole (Microtus ochrogaster) and the aggression that is displayed by both male and female voles toward intruders into their territory. We have documented that voles which repeatedly lose aggressive encounters display an avoidance of social interactions involving exposure to unfamiliar individuals, mimicking symptomatology of social anxiety disorder in humans.

A burgeoning amount of evidence indicates that individual susceptibility to social defeat in rodents may be due to disturbances to the neural activity in many brain regions associated with the mesolimbic dopamine reward circuit, such as the ventral tegmental area, nucleus accumbens, amygdala, and prefrontal cortex. Our research group is using genetically encoded calcium-indicators with in vivo high-resolution cellular imaging of defined neural populations within multiple fields of view in freely moving animals, known as multi-channel fiber photometry. This means the neural activity of a network of brain regions can be simultaneously recorded during behavioral assessments. We can utilize optogenetic tools as well as site-specific pharmacology to manipulate the inputs to determine a causal relationship between aberrant mesolimbic connectivity and behavioral responses to social conflict.

In addition, the success of selective serotonin reuptake inhibitors (SSRIs) in treating social anxiety disorder suggests that dysregulation of the serotonin neurotransmitter systems may play a role, though this treatment may adversely affect signaling of other neurochemicals such as the neuropeptide oxytocin. A few neuroimaging studies in individuals experiencing social anxiety disorder have documented disruption of serotonin and oxytocin receptor function, particularly in limbic and paralimbic regions. Still, research exploring the casual relationship between serotonin and oxytocin brain function and social approach/avoidance response that characteristics social anxiety is sparse. Our group is conducting behavioral pharmacology studies within our social defeat paradigm to better understand the serotonin and oxytocin regulation of social approach/avoidance response after defeat conditioning. 

Neurocircuitry governing the protective effects of social bonds

Social support can ameliorate stress-induced biobehavioral responses and reduce the risk of subsequent mental disorders. This stress buffering is dependent on relationship intimacy. Therefore, support from strong social bonds, such as a romantic partner, has a greater effect in reducing the negative impact of stress (e.g., suffering from a panic disorder or psychological distress) than support from less intimate ties. Still, the neuroendocrine mechanisms through which social buffering occurs is not well understood. Our previous work identified a local social buffering circuit in the hypothalamus in which partners reduced stress physiology and behavior through an increased oxytocin-GABA inhibitor signal to CRH neurons that catalyzes the hypothalamic-pituitary-adrenal axis response. Still, more work needs to be conducted in this area to explore other neural circuits involved in promoting the social buffering effect. Our current work has implicated dopamine activity in the amygdala as a neural signal which promotes social avoidance after conflict. We are studying the functionality of an amygdaloidal dopamine circuit within the context of social buffering by evaluating the effects of contact with a social partner after conflict on dopamine signaling and social approach/avoidance behaviors.

Neurobiology of Social Loss

With over 800,000 new widows and widowers in the United States annually, spousal bereavement is a significant cause of psychiatric and medical morbidity, and includes psychiatric sequelae such as depression, anxiety, substance abuse, and complicated grief. Thus, understanding the behavioral pathologies and neuroendocrine mechanisms that underlie the challenges to mental health and normal behavioral routines associated with social loss are important to improve treatment of subsequent mental disorders. The monogamous prairie vole (Microtus ochrogaster) is a rodent species that forms pair bonds between breeding partners and has been used to study the neurobiology of social behaviors and social isolation. Interestingly, adult male prairie voles do not display robust behavioral abnormalities in result of isolation from a familiar, non-bonded conspecific; however, separation from a bonded female partner can be rather distressing, affecting normal behavioral routines and biological function. Thus, male prairie voles provide a model to characterize the impact that social loss has on normal behavioral routines and function of neuronal systems. Recently, several features of the male prairie vole brain have been identified to be sensitive to social loss and govern behavioral consequences, suggesting an accumbens-centric model where signaling peptides have inversed modulatory inputs. As stated above, the human nucleus accumbens is altered during grief and complicated grief following social loss. Our current work is using optogenetics and pharmacology to explore a theoretical neurocircuit of social loss, featuring oxytocin and corticotrophin-releasing hormone influencing the mesolimbic dopamine regulation of behavioral symptoms of social loss

The Prairie Vole (Microtus ochrogaster)