The Three Musketeers in the Medial Prefrontal Cortex: Subregion-specific Structural and Functional Plasticity Underlying Fear Memory Stages

Fear memory recruits various brain regions with long-lasting brain-wide subcellular events. The medial prefrontal cortex processes the emotional and cognitive functions required for adequately handling fear memory. Several studies have indicated that subdivisions within the medial prefrontal cortex, namely the prelimbic, infralimbic, and anterior cingulate cortices, may play different roles across fear memory states. Through a dedicated cytoarchitecture and connectivity, the three different regions of the medial prefrontal cortex play a specific role in maintaining and extinguishing fear memory. Furthermore, synaptic plasticity and maturation of neural circuits within the medial prefrontal cortex suggest that remote memories undergo structural and functional reorganization. Finally, recent technical advances have enabled genetic access to transiently activated neuronal ensembles within these regions, suggesting that memory trace cells in these regions may preferentially contribute to processing specific fear memory. We reviewed recently published reports and summarize the molecular, synaptic and cellular events occurring within the medial prefrontal cortex during various memory stages.