Structural, Synaptic, and Epigenetic Dynamics of Enduring Memories

Abstract

Our memories are the records of the experiences we gain in our everyday life. Over time, they slowly transform from an initially unstable state into a long-lasting form. Many studies have been investigating from different aspects how a memory could persist for sometimes up to decades. In this review, we highlight three of the greatly addressed mechanisms that play a central role for a given memory to endure: the allocation of the memory to a given neuronal population and what brain areas are recruited for its storage; the structural changes that underlie memory persistence; and finally the epigenetic control of gene expression that might regulate and support memory perseverance. Examining such key properties of a memory is essential towards a finer understanding of its capacity to last.

Figure 1

Schematic illustrating three essential mechanisms that might contribute to remote memory storage and thus memory endurance in the (rodent) brain, which are discussed in this review. First, during memory allocation, learning induces the activity of a specific subpopulation of cells—likely spread across different brain areas—which will become recruited into the memory trace. The amygdala (AMY), the hippocampus (HPC), and the prefrontal cortex (PFC) are known to be activated during memory allocation (for details see text). Second, in cells allocated to a specific memory—also known as the memory engram [–3]—structural changes at the level of dendritic spines have been demonstrated by several studies. These changes are exclusive to the cells of the memory trace or engram (red) but not observed in other cells (grey) [53]. Third, memory engram cells are also likely to be characterized by epigenetic changes, such as posttranslational modifications (PTMs) on histone proteins, and methylation of the DNA, the core chromatin constituents. Note, however, that such engram-specific engagement of epigenetic mechanisms remains to be experimentally demonstrated.

Box 1

Recent insights into structural plasticity and remote fear memory extinction.

Box 2

Recent insights into epigenetic dynamics of remote memory attenuation.