Altered visual cortical processing in a mouse model of MECP2 duplication syndrome

Dinghong Zhang,Jing Liu,Taorong Xie,Haishan Yao,Ran Zhang,Bin Yu,Dali Tong,Weiqian Jiang,Zilong Qiu

doi:10.1038/s41598-017-06916-3

Abstract

As an epigenetic modulator of gene expression, Methyl-CpG binding protein 2 (MeCP2) is essential for normal neurological function. Dysfunction of MeCP2 is associated with a variety of neurological disorders. MECP2 gene duplication in human causes neuropsychiatric symptoms such as mental retardation and autism. MeCP2 overexpression in mice results in neurobehavioural disorders, dendritic abnormalities, and synaptic defects. However, how gain of MeCP2 function influences cortical processing of sensory information remains unclear. In this study, we examined visual processing in a mouse model of MECP2 duplication syndrome (MECP2 Tg1 mouse) at 8 and 14 weeks, which were before and after the onset of behavioural symptoms, respectively. In vivo extracellular recordings from primary visual cortex (V1) showed that neurons in Tg1 mice at both adult ages preferred higher spatial frequencies (SFs) than those in wild-type (WT) littermate controls, and the semi-saturation contrasts of neurons were lower in Tg1 mice at 8 weeks but not at 14 weeks. Behavioural experiments showed that the performance for visual detection at high SFs and low contrasts was higher in MECP2 Tg1 mice. Thus, MeCP2 gain-of-function in mice leads to higher visual acuity and contrast sensitivity, both at the levels of cortical response and behavioural performance.

Highlights

Methyl-CpG binding protein 2 (MeCP2), a key epigenetic modulator of gene expression, is widely expressed in the developing and mature brain[1, 2]
By training mice to perform visual detection of stimuli that varied in spatial frequencies (SFs) or contrasts, we found that MECP2 Tg1 mice exhibited higher behavioral performance in detecting stimuli at high SFs or at low contrasts
We found that a prominent effect of MeCP2 overexpression in Tg1 mice was the enhanced visual acuity of V1 neurons

Summary

Introduction

Methyl-CpG binding protein 2 (MeCP2), a key epigenetic modulator of gene expression, is widely expressed in the developing and mature brain[1, 2]. Mouse models with MECP2 mutations show progressive neurological dysfunctions recapitulating the symptoms in Rett syndrome[3]; progressive neurological disorders are found in mice that express MeCP2 at twice the wild-type levels via transgenic insertion of the human MECP2 gene (MECP2 Tg1 mice) or mice that overexpress the mouse MECP2 gene in neurons[9, 10] Both loss and gain of MeCP2 function lead to abnormalities of the nervous system. We performed in vivo electrophysiological recordings to examine the visual response properties of V1 neurons in MECP2 Tg1 mice at two different adult ages, which were before and after the age of symptomatic onset at 10–12 weeks[9], respectively At both ages examined, V1 neurons in Tg1 mice exhibited higher spatial frequency (SF) preference compared to those in wild-type (WT) littermates, indicating that MeCP2 overexpression increases the visual acuity of V1 neurons both before and after the onset of behavioural symptoms. Our results demonstrate that MeCP2 overexpression enhances the sensitivity of visual cortical neurons to high SFs and low contrasts, leading to enhanced behavioural performance in detecting stimuli with high SFs and low contrasts

Methods

Results

Conclusion