Epigenetic mechanisms of memory formation and reconsolidation

Abstract

Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation.

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

“…For example, ERK phosphorylation appears to regulate histone acetylation (Levenson et al 2004). Over the past decade, it has become clear that epigenetic processes such as histone acetylation and DNA methylation are important regulators of learning and memory mediated by numerous brain regions including the hippocampus (for recent reviews, see Sweatt 2009;Sweatt 2010, 2011;Fischer et al 2010;Gräff and Tsai 2013;Peixoto and Abel 2013;Jarome and Lubin 2014). Given the importance of ERK activation to estrogenic regulation of memory consolidation, our laboratory conducted a series of studies to examine whether histone acetylation and DNA methylation were involved in the effects of E 2 on memory consolidation in ovariectomized mice.…”

Memory Impairment Induced by Borna Disease Virus 1 Infection is Associated with Reduced H3K9 Acetylation

“…Memory formation and synaptic plasticity have been shown to be associated with changes in histone acetylation [13]. Aberrant activity of histone acetyl transferases (HATs) or histone deacetylases (HDACs) can alter the levels of acetylated histones and cause abnormal gene expression [14,15].…”

Epigenetic regulation of Fgf1 transcription by CRTC1 and memory enhancement

“…Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to re-stabilize (Nader et al, 2000; Suzuki et al, 2004). It should be noted that chromatin histone modifications are suggested to be involved not only in memory consolidation but also in memory reconsolidation (Hemstedt et al, 2017; Jarome and Lubin, 2014; Lattal and Wood, 2013). Importantly, CRTC1 overexpression enhanced both memory consolidation and reconsolidation (Sekeres et al, 2012).…”