Fear Expression Suppresses Medial Prefrontal Cortical Firing in Rats.

Abstract

The medial prefrontal cortex (mPFC) plays a crucial role in emotional learning and memory in rodents and humans. While many studies suggest a differential role for the prelimbic (PL) and infralimbic (IL) subdivisions of mPFC, few have considered the relationship between neural activity in these two brain regions recorded simultaneously in behaving animals. Importantly, how concurrent PL and IL activity relate to conditioned freezing behavior is largely unknown. Here we used single-unit recordings targeting PL and IL in awake, behaving rats during the acquisition and expression of conditioned fear. On Day 1, rats received either signaled or unsignaled footshocks in the recording chamber; an auditory conditioned stimulus (CS) preceded signaled footshocks. Twenty-four hours later, animals were returned to the recording chamber (modified to create a novel context) where they received 5 CS-alone trials. After fear conditioning, both signaled and unsignaled rats exhibited high levels of post-shock freezing that was associated with an enduring suppression of mPFC spontaneous firing, particularly in the IL of signaled rats. Twenty-four hours later, CS presentation produced differential conditioned freezing in signaled and unsignaled rats: freezing increased in rats that had received signaled shocks, but decreased in animals in the unsignaled condition (i.e., external inhibition). This group difference in CS-evoked freezing was mirrored in the spontaneous firing rate of neurons in both PL and IL. Interestingly, differences in PL and IL firing rate highly correlated with freezing levels. In other words, in the signaled group IL spontaneous rates were suppressed relative to PL, perhaps limiting IL-mediated suppression of fear and allowing PL activity to dominate performance, resulting in high levels of freezing. This was not observed in the unsignaled group, which exhibited low freezing. These data reveal that the activity of mPFC neurons is modulated by both associative and nonassociative stimuli that regulate conditioned fear.