Abstract
Fragile X Syndrome (FXS), the most common inherited form of human intellectual disability (ID) associated with autistic-like behaviors, is characterized by dys-sensitivity to sensory stimuli, especially vision. In the absence of Fragile Mental Retardation Protein (FMRP), both retinal and cerebral structures of the visual pathway are impaired, suggesting that perception and integration of visual stimuli are altered. However, behavioral consequences of these defects remain unknown. In this study, we used male Fmr1−/y mice to further define visual disturbances from a behavioral perspective by focusing on three traits characterizing visual modality: perception of depth, contrasts and movements. We performed specific tests (Optomotor Drum, Visual Cliff) to evaluate these visual modalities, their evolution from youth to adulthood, and to assess their involvement in a cognitive task. We show that Fmr1−/y mice exhibit alteration in their visual skills, displaying impaired perspective perception, a drop in their ability to understand a moving contrasted pattern, and a defect in contrasts discrimination. Interestingly, Fmr1−/y phenotypes remain stable over time from adolescence to late adulthood. Besides, we report that color and shape are meaningful for the achievement of a cognitive test involving object recognition. Altogether, these results underline the significance of visual behavior alterations in FXS conditions and relevance of assessing visual skills in neuropsychiatric models before performing behavioral tasks, such as cognitive assessments, that involve visual discrimination.
Highlights
Fragile X Syndrome (FXS) is the most common inherited form of human intellectual disability (ID) affecting approximately 1 in 4,000 males (Penagarikano et al, 2007; Abrahams and Geschwind, 2008; Hunter et al, 2014)
Using the validated murine FXS model employing Fmr1−/y mouse strain (Bakker et al, 1994), we have shown that Fragile X Mental Retardation Protein (FMRP) deficiency in the retina generates significant abnormalities in proteins contents and cellular alterations leading to defected signal transmission between photoreceptor cells and the inner retina, measured by the electroretinogram (ERG) technique (Rossignol et al, 2014; Perche et al, 2018)
Motion and contrast understanding of Fmr1−/y mice were investigated thanks to the Optomotor Drum. This apparatus is based on a natural reflex: a mouse with visual abilities efficient enough to detect a contrasted motion passing through its visual field would have the reflex to follow this stimulus with its head, at least for a brief moment (Mitchiner et al, 1976; Schmucker et al, 2005; Kretschmer et al, 2015)
Summary
Fragile X Syndrome (FXS) is the most common inherited form of human intellectual disability (ID) affecting approximately 1 in 4,000 males (Penagarikano et al, 2007; Abrahams and Geschwind, 2008; Hunter et al, 2014). This X-linked disorder is characterized by moderate to severe mental retardation, autistic-like behavior, facial abnormalities and macroorchidism. FXS patients present abnormal sensory processing named sensory hypersensitivity (Minshew et al, 1997; Baron-Cohen et al, 2009), characterized by early life strong aversion for visual social contact (over 90% of FXS children), tactile contact or increased noise sensitivity (Lachiewicz et al, 1994; Merenstein et al, 1996)
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