A Mouse Model of Visual Perceptual Learning Reveals Alterations in Neuronal Coding and Dendritic Spine Density in the Visual Cortex.

Yan Wang,Jing Peng,Xu Hu,Xiao Ma,Hui Liu,Yue Li,Xu An,Xian Zhang,Wei Wu,Yupeng Yang,Shihao Lou,Danyi Ma,Yifeng Zhou

doi:10.3389/fnbeh.2016.00042

Abstract

Visual perceptual learning (VPL) can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF) for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS) and a 55% gain in visual acuity (VA). Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1) than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

Highlights

Visual perceptual learning (VPL) refers to significant and long-lasting improvements in visual performance resulting from repetitive training on a visual task such as grating orientation discrimination (Goldstone, 1998; Gilbert et al, 2001; Lu et al, 2011)
Two-way mixed-design ANOVA with the group as a between-subjects factor and test (Pre vs. Post) as a within-subjects factor revealed significant effects of the group [F(1,19) = 44.885, p < 0.001], test [F(1,19) = 75.479, p < 0.001], and their interaction [F(1,19) = 52.568, p < 0.001]. These results indicated a greater benefit for contrast sensitivity (CS) in the near the individual contrast threshold (NCT) group than in the control group over the course of training
Because the control mice were matched to the NCT mice in terms of overall swim time in the visual water maze, their lack of improvement in CS and visual acuity (VA) indicates that the physical exercise component associated with a simple visual discrimination task does not contribute to the improvement in spatial vision

Summary

Introduction

Visual perceptual learning (VPL) refers to significant and long-lasting improvements in visual performance resulting from repetitive training on a visual task such as grating orientation discrimination (Goldstone, 1998; Gilbert et al, 2001; Lu et al, 2011). VPL has been considered one of the most promising rehabilitative approaches for visually impaired populations, especially adult amblyopia (Polat et al, 2004; Levi, 2005; Zhou et al, 2006). Full recovery of degraded VA in adult amblyopic patients using VPL remains a challenge. A better understanding of the mechanisms underlying VPL is important for developing more effective treatments for adult amblyopia. Experimental animal models are important for understanding the neurobiological basis of VPL and for the development of therapeutic interventions. Much of the current understanding of the neural mechanisms underlying VPL is derived from studies of humans and large mammalian models, such as monkeys and cats. Elucidation of the cellular and molecular mechanisms underlying VPL remains challenging

Methods

Results

Conclusion