Encoding of conditioned inhibitors of fear in the infralimbic cortex

Cues in the environment signaling the absence of threat, i.e. safety, can influence both fear and reward-seeking behaviors. Heightened and maladaptive fear is associated with reduced activity in the medial prefrontal cortex. We have previously shown in male rats that the infralimbic (IL) prefrontal cortex is necessary for suppressing fear during a safety cue. The objective of the present study was to determine if there was safety cue-specific neural activity within the IL using a Pavlovian conditioning paradigm, where a fear cue was paired with shock, a safety cue was paired with no shock, and a reward cue was paired with sucrose. To investigate how safety cues can suppress fear, the fear and safety cues were presented together as a compound fear + safety cue. Single-unit activity showed a large proportion of neurons with excitatory responses to the fear + safety cue specifically, a separate group of neurons with excitatory responses to both the reward and fear + safety cues, and bidirectional neurons with excitation to the fear + safety cue and inhibition to the fear cue. Neural activity was also found to be negatively correlated with freezing during the fear + safety cue. Together, these data implicate the IL in encoding specific aspects of conditioned inhibitors when fear is being actively suppressed.