DNA methylation, plasticity, behaviour

DNMT enzymes methylate DNA. This paper shows the role of DNA methylation in plasticity, learning, memory, emotional behaviour, fear-related memory and drug addiction.

“For instance the double, but not the single, knock-out (KO) mouse model of Dnmt3a and Dnmt1 in forebrain excitatory neurons shows impairment in hippocampal plasticity and learning and memory (Feng et al., 2010), suggesting redundant activity of these DNMT in mature neurons.

Furthermore, DNMT1 and DNMT3a have been demonstrated to be the protagonists of a variety of different forms of neuronal plasticity in the adult, such as fear-related memory (Miller and Sweatt, 2007), drug addiction and emotional behavior (LaPlant et al., 2010), and age associate decline in cognitive abilities (Oliveira et al., 2012).” (R1)

Memory formation depends on methylation

“Here we report that DNMT gene expression is upregulated in the adult rat hippocampus following contextual fear conditioning and that DNMT inhibition blocks memory formation.

In addition, fear conditioning is associated with rapid methylation and transcriptional silencing of the memory suppressor gene PP1 and demethylation and transcriptional activation of the synaptic plasticity gene reelin, indicating both methyltransferase and demethylase activity during consolidation.

DNMT inhibition prevents the PP1 methylation increase, resulting in aberrant transcription of the gene during the memory-consolidation period.

These results demonstrate that DNA methylation is dynamically regulated in the adult nervous system and that this cellular mechanism is a crucial step in memory formation.” (R2)