Editorial: Genetic, Epigenetic, and Epitranscriptomic Mechanisms Associated With Learning and Memory

The formation of long-term memory requires activity-dependent gene expression and protein translation, which allow the neurons to dynamically adjust their synaptic strength during learning (Martin et al., 2000; Sutton and Schuman, 2006). One of the best-studied forms of synaptic plasticity is long-term potentiation (LTP), which produces a persistent increase in the synaptic strength of neurons (Martin et al., 2000). It is well established that messenger RNAs (mRNAs) and proteins must be synthesized to maintain the long-lasting increase in the magnitude of the synaptic response and memory consolidation (Hernandez and Abel, 2008; Yap and Greenberg, 2018). To date, large collections of genes have been associated with learning and memory processes (Knowles et al., 2014; Reshetnikov et al., 2020). Yet new gene transcription alone cannot justify the dynamic and long-term sustainability often observed with learning and memory. But how are these synaptic changes, which arise during learning, subsequently retained throughout life? For example, how does one remember to ride a bicycle after years of nonuse? How does our brain store and retain this information at the molecular level? The traditional view of nature (i.e., genes) versus nurture (i.e., environment and experience) as two separate entities has been challenged over the past two decades by evidence of a direct and dynamic relationship between genes and environmental stimuli (Tsankova et al., 2007; Guan et al., 2015). Epigenetic regulation is the process by which the activity of a particular gene is controlled by the structure of nearby chromatin (Tsankova et al., 2007). This can occur via chromatin remodeling and involves histone modifications, DNA methylation and the binding of numerous transcription factors and transcriptional co-activators and co-repressors all of which are thought to play a critical role in retaining long-term changes in post-mitotic cells. Epigenetic regulation was originally highlighted to be crucial for nervous system development, but has also been identified in the mature brain and may underlie stables changes in gene expression both under normal conditions and in several neuropathological states. In the example of learning and memory, different epigenetic regulators work in concert to converge the upstream signaling cascade and manipulate downstream gene transcription with precise timing. In addition to epigenetic modifications, the emerging field of epitranscriptomics (RNA modifications) has also rapidly shifted our views on the mechanisms that regulate gene expression (Leighton et al., 2018; Widagdo et al., 2021). Following de novo gene expression, both mRNAs and non-coding RNAs (ncRNAs) (e.g., circular RNAs and micro RNAs) undergo further processing, including splicing, polyadenylation and nuclear export to ensure their proper expression, localization or translational control in neurons. Together the cross-talk between transcription factors and epigenetic modifiers play an important role in driving Edited and reviewed by: Mojgan Rastegar, University of Manitoba, Canada