Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory?

Abstract

A complete understanding of the fundamental mechanisms of learning and memory continues to elude neuroscientists. Although many important discoveries have been made, the question of how memories are encoded and maintained at the molecular level remains. To date, this issue has been framed within the context of one of the most dominant concepts in molecular biology, the central dogma, and the result has been a protein-centric view of memory. Here we discuss the evidence supporting a role for neuroepigenetic mechanisms, which constitute dynamic and reversible, state-dependent modifications at all levels of control over cellular function, and their role in learning and memory. This neuroepigenetic view suggests that DNA, RNA and protein each influence one another to produce a holistic cellular state that contributes to the formation and maintenance of memory, and predicts a parallel and distributed system for the consolidation, storage and retrieval of the engram.

Keywords: DNA editing; DNA modifications; DNA structure; RNA editing; epigenetics; epitranscriptomics; learning; memory; neuroepigenetics.

Figure 1

Timeline of significant discoveries in the field of cognitive neuroepigenetics.

Figure 2

A neuroepigenetic model of memory suggests dynamic and reversible, state-dependent, modifications on DNA, RNA and protein that occur during consolidation, storage and retrieval. Much like Roberson and Sweatt’s model: X indicates cytosine and X′ 5-mC, Y adenosine and Y′ N6-methyladenosine, Z is acetylated histone and Z′ deacetylated histone. Although more evidence is required to establish the generalized nature of this model across all phases of learning and memory, it is well established that epigenetic mechanisms influence memory storage, and emerging findings suggest an influence on consolidation and retrieval. ^,