Concussive Brain Injury Enhances Fear Learning and Excitatory Processes in the Amygdala

BackgroundMild traumatic brain injury (cerebral concussion) results in cognitive and emotional dysfunction. These injuries are a significant risk factor for the development of anxiety disorders, including posttraumatic stress disorder. However, because physically traumatic events typically occur in a highly emotional context, it is unknown whether traumatic brain injury itself is a cause of augmented fear and anxiety.MethodsRats were trained with one of five fear-conditioning procedures (n = 105) 2 days after concussive brain trauma. Fear learning was assessed over subsequent days and chronic changes in fear learning and memory circuitry were assessed by measuring N-methyl-D-aspartate receptor subunits and glutamic acid decarboxylase, 67 kDa isoform protein levels in the hippocampus and basolateral amygdala complex (BLA).ResultsInjured rats exhibited an overall increase in fear conditioning, regardless of whether fear was retrieved via discrete or contextual-spatial stimuli. Moreover, injured rats appeared to overgeneralize learned fear to both conditioned and novel stimuli. Although no gross histopathology was evident, injury resulted in a significant upregulation of excitatory N-methyl-D-aspartate receptors in the BLA. There was a trend toward decreased γ-aminobutyric acid-related inhibition (glutamic acid decarboxylase, 67 kDa isoform) in the BLA and hippocampus.ConclusionsThese results suggest that mild traumatic brain injury predisposes the brain toward heightened fear learning during stressful postinjury events and provides a potential molecular mechanism by which this occurs. Furthermore, these data represent a novel rodent model that can help advance the neurobiological and therapeutic understanding of the comorbidity of posttraumatic stress disorder and traumatic brain injury.