A number of studies indicate that the medial prefrontal cortex (mPFC) plays a role in mediating the expression of behavioral responses during tasks that require flexible changes in behavior. During trace eyeblink conditioning, evidence suggests that the mPFC provides the cerebellum with a persistent input to bridge the temporal gap between conditioned and unconditioned stimuli. Therefore, the mPFC is in a position to directly mediate the expression of trace conditioned responses (CRs). However, it is unknown whether persistent neural responses are associated with the flexible expression of behavior when task contingencies are changed during trace eyeblink conditioning. To investigate this, single-unit activity was recorded in the mPFC of rabbits during extinction and reacquisition of trace eyeblink conditioning, and during training to a different conditional stimulus. Persistent responses remained unchanged after full extinction, and also did not change during reacquisition training. During training to a different tone, however, the generalization of persistent responses to the new stimulus was associated with an animal’s performance—when persistent responses generalized to the new tone, performance was high (>50% response rate). When persistent responses decreased to baseline rates, performance was poor (<50% response rate). The data suggest that persistent mPFC responses do not appear to mediate flexible changes in the expression of the original learning, but do appear to play a role in the generalization of that learning when the task is modified.
Significance Statement The medial prefrontal cortex (mPFC) plays a role in executive function, controlling the expression or inhibition of behaviors. But it is not clear under what conditions such executive control is observed, or how neural activity in the mPFC might mediate the expression of behavior. Trace eyeblink conditioning is known to rely on mPFC neurons responding persistently to a training cue, and offers an opportunity to test whether changes in the activity of these neurons might mediate changes in behavior when task contingencies are altered. PFC cells continued to respond persistently after extinction training, suggesting that the mPFC may not mediate the inhibition of previous learning. However, the generalization of persistent responses to a new task was associated with successful performance.