Mild concussion impairs extinction of avoidance and alters respective brain circuits in male rats

Concussive brain injury is a risk factor for anxiety disorders. Pre-clinical models demonstrate that concussion increases passive fear responses, such as conditioned freezing, yet provide limited insight to active responses like avoidance of perceived threats. This is important because persistent avoidance is characteristic of anxiety disorders. Moreover, brain injury can induce an imbalance of the gut microbiome, which can alter emotions. Adult male rats were trained on a platform-mediated avoidance task where they learned to step onto a platform to avoid a foot shock following a conditioned auditory tone. A sucrose reward was provided via a lever press that is opposite to the platform. Next, closed head injury was delivered to produce a mild concussion. After recovery, separate cohorts of rats were tested to dissociate between changes in avoidance expression and extinction-related processes. Cellular activity was assessed using c-Fos immunohistochemistry in brain regions implicated in avoidance: amygdala, medial prefrontal cortex, insular cortex, ventral striatum, and ventral hippocampus. Fecal pellets were collected to extract genetic material to identify potential changes in populations of bacteria in the gut microbiome. Closed head injury induced persistent avoidance by impairing extinction. Injured rats showed decreased activity in the basomedial amygdala and the CA1 subregion of the ventral hippocampus, increased activity in the rostral insular cortex and ventral striatum, and no change in the medial prefrontal cortex. Closed head injury did not induce changes in gut microbiota. Understanding mechanisms of concussion-induced avoidance is crucial for developing rehabilitation strategies for mental health disorders impacted by brain injury.