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Ventromedial prefrontal cortex (vmPFC) is thought to provide regulatory control over Pavlovian fear responses and has recently been implicated in appetitive approach behavior, but much less is known about its role in contexts in which appetitive and aversive outcomes can be obtained and avoided, respectively. To address this issue, we recorded from single neurons in vmPFC while male rats performed our combined approach and avoidance task under reinforced and non-reinforced (extinction) conditions. Surprisingly, we found that cues predicting reward modulated cell firing in vmPFC more often and more robustly than cues preceding avoidable shock; in addition, firing of vmPFC neurons was both response (press or no-press) and outcome (reinforced or extinction) selective. These results suggest a complex role for vmPFC in regulating behavior and support its role in appetitive contexts during both reinforced and non-reinforced conditions. SIGNIFICANCE STATEMENT Selecting context-appropriate behaviors to gain reward or avoid punishment is critical for survival. Although the role of ventromedial prefrontal cortex (vmPFC) in mediating fear responses is well established, vmPFC has also been implicated in the regulation of reward-guided approach and extinction. Many studies have used indirect methods and simple behavioral procedures to study vmPFC, which leaves the literature incomplete. We recorded vmFPC neural activity during a complex cue-driven combined approach and avoidance task and during extinction. Surprisingly, we found very little vmPFC modulation to cues predicting avoidable shock, whereas cues predicting reward approach robustly modulated vmPFC firing in a response- and outcome-selective manner. This suggests a more complex role for vmPFC than current theories suggest, specifically regarding context-specific behavioral optimization.

Neural Activity in Ventral Medial Prefrontal Cortex Is Modulated More Before Approach Than Avoidance During Reinforced and Extinction Trial Blocks