Shank3 mutation disrupts affective touch encoding in the dorsal medial prefrontal cortex of Beagle dogs
Year: 2026
Type: preprint
Abstract: Individuals with autism spectrum disorder (ASD) often show aversion to affective touch (AT). However, the neural mechanism of this abnormality in cortices remains poorly understood probably due to the lack of effective animal models. Here, we used a canine model to address this issue by leveraging the intimate dog-human interactions. In a newly-designed heterospecific AT paradigm, we found that dogs carrying mutations in Shank3 , a high-risk gene for ASD, avoided human AT. In vivo single-unit recording analysis showed that AT-evoked oscillations in the dorsal medial prefrontal cortex (dmPFC) were significantly altered in Shank3 mutant dogs. Shank3 mutation also reduced the number of neurons encoding AT in the dmPFC. Importantly, the aversion to AT and altered neural processing in Shank3 mutants were largely rescued by a GABA A receptor antagonist pentylenetetrazole. Together, these findings provide neural mechanisms for abnormal AT processing in ASD and suggest potential biomarkers for therapeutic strategies.
Institutions: Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, University of Chinese Academy of Sciences, Hubei University, University of Lincoln, Chinese Academy of Medical Sciences & Peking Union Medical College, Chinese Institute for Brain Research, Institute of Psychology, Chinese Academy of Sciences, Peking University, Center for Life Sciences, State Key Laboratory of Membrane Biology, National Center for Nanoscience and Technology, Beijing Normal University, State Key Laboratory of Cognitive Neuroscience and Learning
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: G6361193016, G8791874364
OpenAlex ID: W7210270519