Making adaptive changes in behavior in response to environmental change is essential to survival and therefore is likely to be mediated by complex interactions within a network of distributed neural circuits. One brain region that has been implicated in behavioral flexibility is the medial prefrontal cortex (mPFC). Damage to this region causes impairments in executive function, planning, and working memory, which are all important components of behavioral flexibility. Recording studies have shown that single mPFC neurons show elevated firing rates during the delay period of tasks that require the retention of information over a temporal gap, such as delayed-match/nonmatch-to-sample, suggesting that mPFC neurons are involved in working memory. Other studies have shown that mPFC activity shows anticipatory increases in firing rate prior to the execution of a response, suggesting its role in planning imminent actions. The goal ofthe current proposal is to dissociate mPFC involvement in working memory from other functions by comparing the effects of mPFC lesions and the firing patterns of mPFC single neurons between two similar tasks: one that requires working memory and one that does not. Additionally, reversal of these tasks will reveal the role of the mPFC in behavioral flexibility. Finally, we will investigate the interaction between the hippocampus and mPFC by inactivating the hippocampus and concurrently recording mPFC single neurons during task acquisition, performance and reversal. The results will aid in developing a better understanding ofthe role of the mPFC in adaptive behavior, both alone and in conjunction with the hippocampus.

Public Health Relevance

Neurological disorders such as posttraumatic stress disorder (PTSD) and schizophrenia are accompanied by extensive structural and functional changes throughout the brain, posing a challenge to their diagnosis and treatment. Though patients with these disorders have many distinct symptoms, a common feature that they share is a difficulty with incorporating new behavior based on experience, which is most likely due to the structural and functional changes that have been observed in two memory-related structures: the hippocampus and prefrontal cortex (PFC;Meyer-Lindenberg et al., 2005;Bremer, 2006). Understanding the nature ofthe interaction between PFC and hippocampus could lead to the development of therapeutic approaches that focus on enhancing hippocampal-prefrontal communication.

National Institute of Health (NIH)
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Delaware State University
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