Hippocampal-prelimbic coupling during context-dependent extinction retrieval in rats.

After fear conditioning, repeated presentation of the conditioned stimulus (CS) alone produces a context-dependent extinction of learned fear. The hippocampus has a critical role in this process, but the mechanism by which contextual information encoded by the hippocampus leads to fear suppression is unknown. We hypothesize that contextual information encoded by the dorsal hippocampus supports the recall of extinction memory by the medial prefrontal cortex (mPFC). To test this hypothesis, we evaluated the oscillatory coherence and directional coupling of the hippocampus and mPFC during context-dependent extinction retrieval in a previously published experiment. In this experiment, male and female rats were subjected to auditory fear conditioning followed by fear extinction and extinction retrieval procedures. Previous analyses focused on oscillatory coupling during the CS; here, we performed new analyses to assess hippocampal-prefrontal coupling in the context in which extinction occurred. We found that, after extinction, re-exposing the animals to the extinction context produces a marked increase in dorsal hippocampal theta (6-8 Hz) oscillations. This increase was associated with enhanced coherence with the prelimbic (PL), but not the infralimbic (IL), division of the mPFC. Moreover, Granger causality analyses revealed that hippocampal theta oscillations preceded theta in the PL throughout the extinction retrieval session. This effect emerged during exposure to the extinction context and persisted during the presentation of the CSs and the expression of freezing behavior. Interestingly, this pattern of coherence was not observed in the IL. These results reveal that oscillatory coupling between the dorsal hippocampus and PL facilitates the context-dependent retrieval of the extinguished fear memory.