Abstract

We introduce a novel visual-stimuli four-arm maze (ViS4M) equipped with spectrally- and intensity-controlled LED emitters and dynamic grayscale objects that relies on innate exploratory behavior to assess color and contrast vision in mice. Its application to detect visual impairments during normal aging and over the course of Alzheimer’s disease (AD) is evaluated in wild-type (WT) and transgenic APPSWE/PS1∆E9 murine models of AD (AD+) across an array of irradiance, chromaticity, and contrast conditions. Substantial color and contrast-mode alternation deficits appear in AD+ mice at an age when hippocampal-based memory and learning is still intact. Profiling of timespan, entries and transition patterns between the different arms uncovers variable AD-associated impairments in contrast sensitivity and color discrimination, reminiscent of tritanomalous defects documented in AD patients. Transition deficits are found in aged WT mice in the absence of alternation decline. Overall, ViS4M is a versatile, controlled device to measure color and contrast-related vision in aged and diseased mice.

Highlights

  • We introduce a novel visual-stimuli four-arm maze (ViS4M) equipped with spectrally- and intensitycontrolled light-emitting diode (LED) emitters and dynamic grayscale objects that relies on innate exploratory behavior to assess color and contrast vision in mice

  • We evaluated different aspects of spontaneous behavior that could indicate arm preference (% entries and % time spent in the colored arms) or discrimination that could shed light on visual impairments related to Alzheimer’s disease (AD) pathology and damage to the retina

  • We developed a behavioral visual-stimuli four-arm maze (ViS4M) to assess color vision and contrast sensitivity in mice and applied it in the context of normal aging and AD

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Summary

Introduction

We introduce a novel visual-stimuli four-arm maze (ViS4M) equipped with spectrally- and intensitycontrolled LED emitters and dynamic grayscale objects that relies on innate exploratory behavior to assess color and contrast vision in mice. Visual impairments are among the earliest symptoms documented in AD patients, especially loss of contrast ­sensitivity[54,59,62,63,64,65] and altered color vision reminiscent of tritanomaly, an abnormality of blue-sensitive retinal ­cones[49,59,65,66,67]. True S-cones, containing only S-opsin and implicated in color discrimination in m­ ice[75,85,86], are sparse in the dorsal retina, but account for ~ 30% of the cone population in the ventral ­retina[87] This suggests that in mice, color discrimination and wavelength-specific luminance contrast sensitivity may differ with retinotopic l­ocation[74,88]

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