Microtopography of fear memory consolidation and extinction retrieval within prefrontal cortex and amygdala

Rationale: The precise neural circuitry that encodes fear memory and its extinction within the brain are not yet fully understood. Fearful memories can be persistent, resistant to extinction, and associated with psychiatric disorders, especially post-traumatic stress disorder (PTSD). Here, we investigated the microtopography of neurons activated during the recall of an extinguished fear memory, as well as the influence of time on this microtopography. Methods: We used the plasticity-related phosphorylated mitogen-activated protein kinase (pMAPK) to identify neurons activated in the recall of consolidated and extinguished auditory Pavlovian fear memories in rats. Quantitatively matched brain regions were used to investigate activity in the amygdala and prefrontal cortex. Results: Recall of a consolidated, nonextinguished auditory fear memory resulted in a significantly greater number of activated neurons located in the dorsolateral subdivision of the lateral amygdala (LADL) when recalled 24 h after consolidation but not when recalled 7 days later. We found that the recall of an extinction memory was associated with pMAPK activation in the ventrolateral subdivision of the lateral amygdala (LAVL). Next, we showed that the pattern of pMAPK expression in the prelimbic cortex differed spatially following temporal variation in the recall of that memory. The deep and superficial layers of the pre-limbic cortex were engaged in recent recall of a fear memory, but only the superficial layers were recruited if the recall occurred 7 days later. Conclusions: Collectively, our findings demonstrate a functional microtopography of auditory fear memory during consolidation and extinction at the microanatomical level within the lateral amygdala and medial prefrontal cortex.