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

Shu Juan Puang,Judy C.G Sng,Bavani Elanggovan,Tendy Ching

doi:10.1042/ns20190147

Abstract

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.

Highlights

Neuronal circuits that process sensory information are shaped by patterns of cellular activity during early brain development called critical periods or CPs [1]
As dendritic spine dynamics is widely assumed to be the cellular basis for synaptic plasticity [32,33], we carried out Golgi-cox staining to visualize the dendritic morphology and dendritic spines in primary visual cortex (V1) of standard condition (SC) and EE mice
It can be seen that EE dramatically increases the total and basolateral spine density with a significant increase in the apical spine density in the visual cortex of juveniles raised in EE but not in those raised in SC (Figure 1B, bottom panel)

Summary

Introduction

Neuronal circuits that process sensory information are shaped by patterns of cellular activity during early brain development called critical periods or CPs [1]. Visual cortical circuits exhibit maximal plasticity during CP, but this plasticity is lost by adulthood [1] The loss of this extraordinary plasticity may reflect sequential locks placed on a molecular pathway as the visual cortex consolidates into a structurally elaborated circuitry. The visual system is highly amenable and is manipulated either by decreasing external sensory experience or by dark rearing and monocular deprivation or increasing external stimuli by environmental enrichment. In the latter paradigm, animals are reared in big cages filled with toys, running wheels, tunnels and nesting materials.

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Results

Conclusion