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.
Highlights
The understanding of memory processes in the brain has been at the heart of neuroscience research for more than a century, and a lot has been discovered since
The first hint suggesting that the medial prefrontal cortex (mPFC) is already involved early on originates from long-term potentiation (LTP) recordings after auditory fear conditioning (AFC) in rats: Doyère and colleagues demonstrated that fear memory encoding elicited LTP in the CA1 to Prelimblic Cortex (PL) projection already 20 min after training [52]
Engram cells have been found in the hippocampal formation (HPC) [3,39,89,90] and amygdala [31,91] and in other cortical areas, such as the retrosplenial cortex (RSP)
Summary
The understanding of memory processes in the brain has been at the heart of neuroscience research for more than a century, and a lot has been discovered since. This role was recently supported by the discovery of engram cells in the HPC These neurons are first activated during the initial learning phase, undergo enduring molecular changes (cellular consolidation), and are reactivated during the recall of that same memory. The medial prefrontal cortex (mPFC, see Box 1 for definition) was reported to be necessary for the recall of remote fear memories [6,7]. These findings gave rise to the classical model of memory formation, which posits that the initial formation and storage relies on the HPC, and that the mPFC is only recruited for longer storage [8]. With findings showing that the HPC was primarily required at early recall [1,50,51], this led to and underscored the classical dogma of memory formation, called the standard theory of memory consolidation [8] ( see the discussion below)
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