Brain Injury Induced Prefrontal Cortex Circuit Dysfunction Contributes to Working Memory Impairment

Traumatic Brain Injury (TBI) is the most common cause of brain damage resulting in disability, both in the United States and worldwide. TBI patients suffer from profound impairments in memory function. Lateral fluid percussion injury (LFPI) is the most common animal model of TBI and recreates the memory symptoms experienced by TBI survivors. Using a combination of behavioral testing and neurophysiological recording I investigated dysfunction in the brain circuits underlying post-TBI memory impairment in LFPI animals. I demonstrated that LFPI animals suffer from sustained working memory impairment in the first week after brain injury. Additionally, I determined the neurophysiological changes to the medial prefrontal cortex, a key component of the circuitry underlying working memory. The medial prefrontal cortex displays layer-specific changes to synaptic transmission and intrinsic excitability as well as decreased network excitability after brain injury. This pattern of physiological changes is similar to post-TBI alterations in the hippocampus, another key structure underlying post-TBI memory impairment. Despite the relative lack of attention paid to the medial prefrontal cortex by the TBI field, functional changes in the medial prefrontal cortex after TBI are likely a post-TBI substrate of working memory impairment.