Abstract
The ability to capture the most relevant information from everyday experiences without constantly learning unimportant details is vital to survival and mental health. While decreased activity of the medial prefrontal cortex (mPFC) is associated with failed or inflexible encoding of relevant events in the hippocampus, mechanisms used by the mPFC to discern behavioral relevance of events are not clear. To address this question, we chemogenetically activated excitatory neurons in the mPFC of male rats and examined its impact on local network activity and differential associative learning dependent on the hippocampus. Rats were exposed to two neutral stimuli in two environments whose contingency with an aversive stimulus changed systematically across days. Over 2 weeks of differential and reversal learning, theta band activity began to ramp up toward the expected onset of the aversive stimulus, and this ramping activity tracked the subsequent shift of the set (stimulus modality to environment) predictive of the aversive stimulus. With chemogenetic mPFC activation, the ramping activity emerged within a few sessions of differential learning, which paralleled faster learning and stronger correlations between the ramping activity and conditioned responses. Chemogenetic mPFC activity, however, did not affect the adjustment of ramping activity or behavior during reversal learning or set-shifting, suggesting that the faster learning was not because of a general enhancement of attention, sensory, or motor processing. Thus, the dynamics of the mPFC network activation during events provide a relevance-signaling mechanism through which the mPFC exerts executive control over the encoding of those events in the hippocampus.