NEURAL BASIS OF RESILIENCE TO CHRONIC SOCIAL STRESS IN MALE MICE

Chronic stress is a major risk factor for pathology. In modern life, stress often arises from low socioeconomic status or interpersonal conflict and constitutes a major risk factor for the development of depression and anxiety disorders. Stress resilience is defined as the maintenance or rapid recovery of mental health under adversity. Two key features of resilience in humans are threat-safety discrimination and responsiveness to extinction of fear memories.
In rodent models, after chronic social defeat (CSD) in male mice, some animals discriminate between aggressive conspecifics and safe ones (resilient) while others display generalization of social avoidance (susceptible). At the neural level, social stress activates mesolimbic dopamine (DA) systems and influences learning and memory. In CSD, phasic firing of DA neuron in the nucleus accumbens (NAc) induces social avoidance, whereas inhibition of this firing promotes interaction. However, the role of accumbal dopamine in threat-safety discrimination and extinction of fear memories remains unclear.
Here, we use the genetically encoded DA sensor, dLight1.2, to record DA activity in NAc shell and core during CSD, a post-CSD social threat-safety discrimination test, and extinction of social avoidance in male mice. We found that DA release patterns differed between the NAc shell and core following CSD. Compared with animals that did not learn to avoid aggressive conspecifics, animals that acquired avoidance behavior exhibited elevated DA release at the onset of attacks specifically in the NAc shell. In our ongoing work, we are exploring the relationship between accumbal DA release and the two key features of resilience.