The Medial Prefrontal Cortex and Fear Memory: Dynamics, Connectivity, and Engrams

Abstract

It is becoming increasingly apparent that long-term memory formation relies on a distributed network of brain areas. While the hippocampus has been at the center of attention for decades, it is now clear that other regions, in particular the medial prefrontal cortex (mPFC), are taking an active part as well. Recent evidence suggests that the mPFC-traditionally implicated in the long-term storage of memories-is already critical for the early phases of memory formation such as encoding. In this review, we summarize these findings, relate them to the functional importance of the mPFC connectivity, and discuss the role of the mPFC during memory consolidation with respect to the different theories of memory storage. Owing to its high functional connectivity to other brain areas subserving memory formation and storage, the mPFC emerges as a central hub across the lifetime of a memory, although much still remains to be discovered.

Keywords: connectivity; engrams; fear memory; mPFC.

Figure 1

mPFC inputs are involved in encoding and recent recall of fear memories. Left: Anatomically defined inputs to the mPFC. Right: mPFC inputs functionally involved during fear memory consolidation, color coded by the phase of the memory (blue: encoding, green: recent recall, red: remote recall). Note the absence of functionally characterized mPFC inputs at the time of remote recall. AFC: Auditory fear conditioning; CFC: Contextual fear conditioning; IA: Inhibitory avoidance; MEC: Medial entorhinal cortex; BLA: Basolateral amygdala.

Figure 2

mPFC outputs are involved in recalling fear memories. Left: Anatomically defined outputs from the mPFC. Right: mPFC outputs functionally involved during fear memory consolidation, color coded by the phase of the memory (blue: encoding, green: recent recall, red: remote recall). Note the absence of functionally characterized mPFC outputs at the time of encoding. AFC: Auditory fear conditioning; CFC: Contextual fear conditioning; CPP: Conditioned place preference; BLA: Basolateral amygdala; LHb: Lateral habenula; PAG: Periaqueductal gray; PVT: Paraventricular thalamus; VTA: Ventral tegmental area.