MEF2C and HDAC5 regulate Egr1 and Arc genes to increase dendritic spine density and complexity in early enriched environment.

We investigated the effects of environmental enrichment during critical period of early postnatal life and how it interplays with the epigenome to affect experience-dependent visual cortical plasticity. Mice raised in an EE from birth to during CP have increased spine density and dendritic complexity in the visual cortex. EE upregulates synaptic plasticity genes, Arc and Egr1, and a transcription factor MEF2C. We also observed an increase in MEF2C binding to the promoters of Arc and Egr1. In addition, pups raised in EE show a reduction in HDAC5 and its binding to promoters of Mef2c, Arc and Egr1 genes. With an overexpression of Mef2c, neurite outgrowth increased in complexity. Our results suggest a possible underlying molecular mechanism of EE, acting through MEF2C and HDAC5, which drive Arc and Egr1. This could lead to the observed increased dendritic spine density and complexity induced by early EE.