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. 2019 Oct 2:13:228.
doi: 10.3389/fnbeh.2019.00228. eCollection 2019.

Visual Behavior Impairments as an Aberrant Sensory Processing in the Mouse Model of Fragile X Syndrome

Chloé Felgerolle  1   2 , Betty Hébert  1   2 , Maryvonne Ardourel  1   2 , Géraldine Meyer-Dilhet  1   2 , Arnaud Menuet  1   2 , Kimberley Pinto-Morais  1   2 , Jean-Charles Bizot  3 , Jacques Pichon  1   2 , Sylvain Briault  1   2   4 , Olivier Perche  1   2   4
Affiliations

Visual Behavior Impairments as an Aberrant Sensory Processing in the Mouse Model of Fragile X Syndrome

Chloé Felgerolle et al. Front Behav Neurosci. .

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.

Keywords: FMRP; Fmr1−/y mice; Fragile X Syndrome; contrast sensitivity; depth perception; sensory sensitivity; visual abilities.

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Figures

Figure 1
Figure 1
Apparatuses used to perform behavioral tests. (A) Optomotor Drum device allowing to provide tested mouse with a contrasted moving pattern, in order to assess contrast perception and contrast discrimination. (B) Visual Cliff test assembly composed of a shallow end and a deep end, in order to assess depth perception. (C) Novel Object Recognition (NOR) test. On the left, the different objects used as familiar and novel, and on the right the Open field provided with pairs of objects to test the New Object Recognition.
Figure 2
Figure 2
Creation of contrast-shaded patterns used for an adapted Optomotor Drum. (A) Gray scale created using the Red Green Blue color value (RGB) color system, from black (0;0;0) to white (255;255;255). (B) Contrasted-shaded patterns newly created. (C) RGB details of grays used to compose them and contrast value associated (see “Materials and Methods” section for details on contrast computation).
Figure 3
Figure 3
Optomotor Drum test. Motion and contrast perception of Fmr1−/y mice were investigated thanks to the Optomotor Drum. Histograms represent (A) total time spent in head-tracking (HT), (B) total number of HT, (C) mean duration of one HT and (D) latency to the first HT. Curve represents (E) time spent in HT minute by minute. All data were represent at each age tested (1 month: wild-type (WT) n = 12; Fmr1−/y n = 18; 3 months: WT n = 15; Fmr1−/y n = 13; 6 months: WT n = 14; Fmr1−/y n = 14). All parameters were scored in seconds, and were expressed in % of results obtained with the WT group at the corresponding age (WT littermates). Data represent mean ± SEM. Significant differences between WT and Fmr1−/y are noted by *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.
Figure 4
Figure 4
Contrast-shaded Optomotor Drum test. Contrast discrimination alterations of Fmr1−/y mice were investigated thanks to the Optomotor Drum, with various contrasted conditions. Curve representing (A) total time spent in HT and (B) total number of HT, hence (C) the mean duration of one HT, at each contrast condition (lambda: WT n = 16, Fmr1−/y n = 10; beta: WT n = 7, Fmr1−/y n = 6; gamma: WT n = 10, Fmr1−/y n = 14; omega: WT n = 6, Fmr1−/y n = 7; psi: WT n = 9, Fmr1−/y n = 6). Total durations and mean durations scored in seconds. Total durations and number expressed in % of result of WT mice in lambda condition (standard condition). Data represent mean ± SEM. Significant differences between WT and Fmr1−/y are noted by *p < 0.05; **p < 0.01; ****p < 0.0001. Significant differences between contrast conditions within genotype are noted by #p < 0.05; ##p < 0.01; ####p < 0.0001. Absence of significant difference between groups is noted by ns.
Figure 5
Figure 5
Visual Cliff test. Depth perception in Fmr1−/y mice was assessed with the Visual Cliff test. Histograms represent (A) total time spent in each zone (shallow-end/deep-end), hence (B) the Preference Index (PI) for the shallow end was calculated, and (C) number of occurrences, at both ages tested (3 months: WT n = 25; Fmr1−/y n = 22; 6 months: WT n = 20; Fmr1−/y n = 26). (D) Illustration by a pseudo-colored heat map representing time spent at each position related to the place preference of WT and Fmr1−/y mice. Total durations scored in seconds; index expressed in Arbitrary Unit (AU). Data represent mean ± SEM. Significant differences between WT and Fmr1−/y are noted by *p < 0.05. Significant differences between zones within genotype are noted by #p < 0.05; ##p < 0.01; ####p < 0.0001. Absence of significant difference between groups is noted by ns.
Figure 6
Figure 6
Locomotion parameters in the Visual Cliff test. Locomotion was assessed thanks to total distances moved during the Visual Cliff test in (A) the whole arena, (B) safe and unsafe zones at both ages tested, and thanks to (C) the number of transitions between deep and shallow ends (3 months: WT n = 25; Fmr1−/y n = 22; 6 months: WT n = 20; Fmr1−/y n = 26). Distance scored in centimetre. Data represent mean ± SEM. Significant differences between WT and Fmr1−/y are noted by **p < 0.01; ***p < 0.001. Significant differences between zones within genotype are noted by ##p < 0.01; ####p < 0.0001. Absence of significant difference between groups is noted by ns.
Figure 7
Figure 7
Familiarization phase of the NOR. Fmr1−/y behavior in a cognitive task involving visual modality was evaluated in the standard version of the NOR (NOR1) and two various versions (NOR2 and NOR3). Histograms represent (A) time spent in nose contact with each object and (B) number of visits of each object for each genotype (WT n = 9, Fmr1−/y n = 13), during the familiarization phase. Durations scored in seconds. Data represent mean ± SEM.
Figure 8
Figure 8
Choice phase of the NOR. Histograms represent time spent in nose contact with each object and number of visits, hence a discrimination index for each object, for (A) NOR1, (B) NOR2 and (C) NOR3, for each genotype (WT n = 9, Fmr1−/y n = 13), during the choice phase. Durations scored in seconds; discrimination index expressed in AU. Data represent mean ± SEM. Significant differences between WT and Fmr1−/y are noted by *p < 0.05; **p < 0.01. Absence of significant difference between groups is noted by ns.
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