mPFC and Its Communication with NAc Support Inhibitory Control of Approach Action

Environmental cues associated with rewards, such as food or substances of abuse, often prompt approach and consummatory actions that are difficult to override, even when restraint would be beneficial in the short- or long-term. As such, much research has focused on the neural underpinnings of behavior driven by cues, directed at obtaining reward. However, the neural systems that underlie restraint of behavior in response to reward related cues are not well understood, but play a critical role in maladaptive, impulsive actions. I hypothesized that medial prefrontal cortex (mPFC) and its communication with nucleus accumbens (NAc) play vital roles in such behavioral restraint. I implanted multiwire electrode arrays in the mPFC and recorded the activity of single neurons and characterized firing rate responses to task cues. Neurons in mPFC showed populations of neurons either increased or decreased firing rates transiently in responses to the onset of cues when the animal preformed correctly on both Go and NoGo trials; a small population of neurons showed transient increases that were higher for NoGo compared to Go cues. I then pharmacologically inactivated mPFC and showed that accuracy on NoGo trials was largely reduced. I then used chemogenetics to facilitate firing of mPFC neurons and show increased accuracy on NoGo trials. Together these finding suggest that mPFC is both necessary and sufficient to support inhibitory control on NoGo trials. mPFc sends strong excitatory, glutamatergic connections to NAc. Previous work from our lab showed restraint of approach behavior on NoGo trials was substantially reduced when glutamatergic AMPA/kainite receptors were blocked in NAc, suggesting that excitatory inputs inform NAc to inhibit approach behavior. I hypothesized that mPFC is one origin of the excitatory signal. To investigate this hypothesis, I pharmacologically disconnected the functional communication between mPFC and NAc and found that bilateral and ipsilateral disconnection of mPFC communication with NAc caused an increase in NoGo errors. These results suggest that mPFC signals the appropriate action needed for optimal performance and that NAc integrates this signal to render appropriate approach/withhold behavior.