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. 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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We thank X. Chen and A. Frazier for excellent technical support. This work was supported by the Nancy Lurie Marks Family Foundation and the National Institutes of Health (MH112237) to Z.Y.
The authors declare no competing interests.
Peer review information Nature Protocols thanks T. Takumi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Key references using this protocol
Qin, L. et al. Nat. Neurosci. 21, 564–75 (2018): https://doi.org/10.1038/s41593-018-0110-8
Rein, B. et al Mol. Psychiatry (2020): https://doi.org/10.1038/s41380-020-0693-9
Duffney, L. J. et al. Cell Rep. 11, 1400–1413 (2015): https://doi.org/10.1016/j.celrep.2015.04.064
Supplementary Table 1.
Representative video of a wild type (WT) mouse in the social preference test phase of the three-phase S–NS method, with commentary.
Representative video of a Shank3-deficient mouse in the social preference test phase of the three-phase S–NS method, with commentary.
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Rein, B., Ma, K. & Yan, Z. A standardized social preference protocol for measuring social deficits in mouse models of autism. Nat Protoc 15, 3464–3477 (2020). https://doi.org/10.1038/s41596-020-0382-9
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