Abstract
Pupillary response, an important process in visual perception and social and emotional cognition, has been widely studied for understanding the neural mechanisms of neuropsychiatric disorders. However, there have been few studies on pupil response to social and non-social stimuli in animal models of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder. Here, we developed a pupilometer using a robust eye feature-detection algorithm for real-time pupillometry in dogs. In a pilot study, we found that a brief light flash induced a less-pronounced and slower pupil dilation response in gene-edited dogs carrying mutations in Shank3; mutations of its ortholog in humans were repeatedly identified in ASD patients. We further found that obnoxious, loud firecracker sound of 120 dB induced a stronger and longer pupil dilation response in Shank3 mutant dogs, whereas a high reward food induced a weaker pupillary response in Shank3 mutants than in wild-type control dogs. In addition, we found that Shank3 mutants showed compromised pupillary synchrony during dog-human interaction. These findings of altered pupil response in Shank3 mutant dogs recapitulate the altered sensory responses in ASD patients. Thus, this study demonstrates the validity and value of the pupilometer for dogs, and provides an effective paradigm for studying the underlying neural mechanisms of ASD and potentially other psychiatric disorders.
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Acknowledgements
We thank W. Zhou and Y. Jiang for discussion. This work was supported by grants from The National Key Research and Development Program (2019YFA0707100 and 2021ZD0203901 to Y.Q. Zhang), the Strategic Priority Research Program B of the Chinese Academy of Sciences (XDBS1020100 to Y.Q. Zhang), STI2030-Major Projects (2021ZD0203900 to P.F.Wei), the National Science Foundation of China (31830036 and 31921002 to Y.Q. Zhang, and 32222036 to P. Wei), and the Spring City plan (2022SCP001 to Y.Q. Zhang). The corresponding author (YQZ) had full access to all the data in the study and final responsibility for the decision to submit to publication.
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Y.Z., P.W., L.W., and K.G. conceptualized the project, supervised data collection and analyses. K.H., Q.Y., and W.R. collaborated in designing and constructing the apparatus. K.H. developed the software and algorithm for pupillometry. W.R. and Y.L. performed behavioral experiments, data collection, and analyses. W.R., Y.L. and Y.Z. wrote the manuscript.
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Ren, W., Huang, K., Li, Y. et al. Altered pupil responses to social and non-social stimuli in Shank3 mutant dogs. Mol Psychiatry 28, 3751–3759 (2023). https://doi.org/10.1038/s41380-023-02277-8
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DOI: https://doi.org/10.1038/s41380-023-02277-8