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. 2020 Oct;15(10):3464-3477.
doi: 10.1038/s41596-020-0382-9. Epub 2020 Sep 7.

VSports手机版 - A standardized social preference protocol for measuring social deficits in mouse models of autism

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"VSports最新版本" A standardized social preference protocol for measuring social deficits in mouse models of autism

Benjamin Rein et al. Nat Protoc. 2020 Oct.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and other behavioral abnormalities. The three-chamber social preference test is often used to assess social deficits in mouse models of ASD. However, varying and often contradicting phenotypic descriptions of ASD mouse models can be found in the scientific literature, and the substantial variability in the methods used by researchers to assess social deficits in mice could be a contributing factor. Here we describe a standardized three-chamber social preference protocol, which is sensitive and reliable at detecting social preference deficits in several mouse models of ASD. This protocol comprises three phases that can all be completed within 1 d. The test mouse is first habituated to the apparatus containing two empty cups in the side chambers, followed by the pre-test phase in which the mouse can interact with two identical inanimate objects placed in the cups. During the test phase, the mouse is allowed to interact with a social stimulus (an unfamiliar wild-type (WT) mouse) contained in one cup and a novel non-social stimulus contained in the other cup VSports手机版. The protocol is thus designed to assess preference between social and non-social stimuli under conditions of equal salience. The broad implementation of the three-chamber social preference protocol presented here should improve the accuracy and consistency of assessments for social preference deficits associated with ASD and other psychiatric disorders. .

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Figures

Figure 1.
Figure 1.
Social behavioral data obtained from several transgenic mouse models using the 3-phase S-NS protocol. a, Graphic depicting the 3-phase S-NS protocol, consisting of a 10-minute habituation phase to the apparatus containing two empty cups, a 10-minute pre-test phase in which two identical objects (paper balls) are placed under the cups, and a 10-minute social preference test phase in which one cup contains a social (S) stimulus (age- and sex-matched WT mouse) and the other contains a non-social (NS) stimulus (wooden block). b, e, h, k, n, q, Bar graphs showing the amount of time spent interacting with the social stimulus (S) or non-social stimulus (NS) in male WT vs. Shank3+/ΔC mice (b), female WT vs. Shank3+/ΔC mice (e), WT vs. 16p11.2dp/+ mice (h), WT vs. 16p11.2+/− mice (k), Cul3f/f vs. Cul3f/- mice (n), and WT vs. D4KO mice (q). Both sexes were used in g, j, m, p. c, f, i, l, o, r, Bar graphs comparing the social preference index of individual mouse lines. d, g, j, m, p, Representative heat maps illustrating the topographical time distribution in social preference tests of individual mouse lines. All data are presented as mean ± S.E.M. For all figures, n.s. not significant, *p < 0.05, **p < 0.01, ***p < 0.0001, S vs. NS; #p < 0.05, ##p < 0.01, WT vs. mutant (social time). Note, the results in panels b-d, h-j, and n-p are consistent with prior findings in references 7, 8, 11, 25, 31 and 36. All animal studies were performed with the approval of the Institutional Animal Care and Use Committee (IACUC) of the State University of New York at Buffalo.
Figure 2.
Figure 2.
Social behavioral data obtained from several ASD mouse models using the 2-phase S-E protocol. a, Graphic depicting the 2-phase S-E protocol, consisting of a 10-minute habituation phase to the empty apparatus and a 10-minute social preference test phase in which a social stimulus (age- and sex-matched WT mouse under cup) and non-social stimulus (empty cup) are introduced. b, e, h, Bar graphs showing the amount of time spent interacting with the social stimulus (S) or empty cup (E) in male WT vs. Shank3+/ΔC mice (b), WT vs. 16p11.2dp/+ mice (e), and Cul3f/f vs. Cul3f/- mice (h). Both sexes were used in e and h. c, f, i, Bar graphs comparing the social preference index of individual mouse lines. d, g, j, Representative heat maps illustrating the topographical time distribution in social preference tests of individual mouse lines. All data are presented as mean ± S.E.M. For all figures, n.s. not significant, *p < 0.05, **p < 0.01, ***p < 0.0001. All animal studies were performed with the approval of the Institutional Animal Care and Use Committee (IACUC) of the State University of New York at Buffalo.

References

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