How the epigenome integrates information and reshapes the synapse

Campbell, Rianne R.; Wood, Marcelo A.

doi:10.1038/s41583-019-0121-9

Cited by 130 publications

(93 citation statements)

References 258 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, differential miRNA levels in the hippocampus have been linked to lasting behavioral changes after ENR 15 and could play a role in the observed maintenance of ENR-induced individuality. Since DNA methylation controls many molecular processes, including expression of miRNAs 43 , somatic mosaicism 44 and other epigenetic modifications in the brain 45 , the here identified DNA methylation changes likely interact with other molecular players to facilitate the development and maintenance of individual behavior.…”

Section: Behavioral Individualization As Measured By Increasing Intementioning

confidence: 92%

Early-life environmental enrichment generates persistent individualized behavior in mice

Zocher

Schilling²,

Grzyb³

et al. 2019

Preprint

View full text Add to dashboard Cite

Individuals differ in their response to environmental stimuli, but the stability of individualized behaviors and their associated changes in brain plasticity are poorly understood. We developed a novel model of enriched environment to longitudinally monitor 40 inbred mice exploring 35 connected cages over periods of three to six months. We show that behavioral individuality that emerged during the first three months of environmental enrichment persisted when mice were withdrawn from the enriched environment for three additional months. Behavioral trajectories were associated with stable inter-individual differences in adult hippocampal neurogenesis and persistent epigenetic effects on neuronal plasticity genes in the hippocampus. Using genome-wide DNA methylation sequencing, we show that one third of the DNA methylation changes were maintained after withdrawal from the enriched environment. Our results suggest that, even under the most constraint conditions controlling genes and environment, early-life experiences result in lasting individualized changes in behavior and brain plasticity.

show abstract

Section: Behavioral Individualization As Measured By Increasing Intementioning

confidence: 92%

Early-life environmental enrichment generates persistent individualized behavior in mice

Zocher

Schilling²,

Grzyb³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…It is widely believed that rapid and reversible DNA methylation is essential for the stability of long-term memory but still very little is known how synaptic signals can induce changes in DNA-methylation to elicit enduring alterations in plasticity-related gene expression (Bayraktar & Kreutz, 2018a, b;Campbell & Wood, 2019;Day & Sweatt, 2010;Miller & Sweatt, 2007;Guo et al, 2011). In addition, aberrant DNA methylation has been implicated in neuropsychiatric diseases including schizophrenia, bipolar, and major depression disorders (Bayraktar & Kreutz, 2018;Mill et al, 2008;Murgatroyd et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Synaptic control of DNA-methylation involves activity-dependent degradation of DNMT3a1 in the nucleus

Bayraktar

Yuanxiang

Gomes

et al. 2019

Preprint

View full text Add to dashboard Cite

DNA-methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3a1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit.Interestingly, synaptic NMDAR drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3a1 and results in deficits of promoter methylation of activity-dependent genes, synaptic plasticity as well as memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively the data show that GluN2A containing NMDAR control synapseto-nucleus signaling that links plasticity-relevant signals to activity-dependent DNAmethylation involved in memory formation.

show abstract

“…Epigenetic mechanisms such as DNA methylation have emerged as important regulators of memory consolidation 8 . Rapid and dynamic changes in DNA methylation have been shown to occur in response to neuronal activity.…”

mentioning

confidence: 99%

Neuronal ensemble-specific DNA methylation strengthens engram stability

et al. 2020

View full text Add to dashboard Cite

Memories are encoded by memory traces or engrams, represented within subsets of neurons that are synchronously activated during learning. However, the molecular mechanisms that drive engram stabilization during consolidation and consequently ensure its reactivation by memory recall are not fully understood. In this study we manipulate, during memory consolidation, the levels of the de novo DNA methyltransferase 3a2 (Dnmt3a2) selectively within dentate gyrus neurons activated by fear conditioning. We found that Dnmt3a2 upregulation enhances memory performance in mice and improves the fidelity of reconstitution of the original neuronal ensemble upon memory retrieval. Moreover, similar manipulation in a sparse, non-engram subset of neurons does not bias engram allocation or modulate memory strength. We further show that neuronal Dnmt3a2 overexpression changes the DNA methylation profile of synaptic plasticity-related genes. Our data implicates DNA methylation selectively within neuronal ensembles as a mechanism of stabilizing engrams during consolidation that supports successful memory retrieval.

show abstract

How the epigenome integrates information and reshapes the synapse

Cited by 130 publications

References 258 publications

Early-life environmental enrichment generates persistent individualized behavior in mice

Early-life environmental enrichment generates persistent individualized behavior in mice

Synaptic control of DNA-methylation involves activity-dependent degradation of DNMT3a1 in the nucleus

Neuronal ensemble-specific DNA methylation strengthens engram stability

Contact Info

Product

Resources

About