GPR158 in pyramidal neurons mediates social novelty behavior via modulating synaptic transmission in male mice
Shoupeng Wei,
Jian Jiang,
Dilong Wang,
Jinlong Chang,
Liusuyan Tian,
Xiuyan Yang,
Xiao-Ru Ma,
Jing-Wei Zhao,
Yiming Li,
Shuwen Chang,
Xinjin Chi,
Huiliang Li,
Ningning Li
Affiliations
Shoupeng Wei
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
Jian Jiang
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
Dilong Wang
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
Jinlong Chang
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
Liusuyan Tian
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
Xiuyan Yang
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
Xiao-Ru Ma
Department of Pathology of Sir Run Run Shaw Hospital, and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
Jing-Wei Zhao
Department of Pathology of Sir Run Run Shaw Hospital, and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Center of Cryo-Electron Microscopy, Zhejiang University, Hangzhou, Zhejiang 310058, China
Yiming Li
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China
Shuwen Chang
Shenzhen Neher Neural Plasticity Laboratory, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China
Xinjin Chi
Department of Anesthesiology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China; Corresponding author
Huiliang Li
Wolfson Institute for Biomedical Research, Division of Medicine, Faculty of Medical Sciences, University College London, London WC1E 6BT, UK; Corresponding author
Ningning Li
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China; China-UK Institute for Frontier Science, Shenzhen 518107, China; Corresponding author
Summary: Impairment in social communication skills is a hallmark feature of autism spectrum disorder (ASD). The role of G-protein-coupled receptor 158 (GPR158) in ASD remains largely unexplored. In this study, we observed that both constitutive and cell-/tissue-specific knockouts of Gpr158 in pyramidal neurons or the medial prefrontal cortex (mPFC) result in impaired novelty preference, while sociability remains unaffected in male mice. Notably, the loss of GPR158 leads to a significant decline in excitatory synaptic transmission, characterized by a reduction in glutamate vesicles, as well as the expression and phosphorylation of GluN2B in the mPFC. We successfully rescue the phenotype of social novelty deficits either by reintroducing GPR158 in the mPFC of Gpr158 deficient mice or by chemogenetic activation of pyramidal neurons where Gpr158 is specifically ablated. Our findings indicate that GPR158 in pyramidal neurons plays a specific role in modulating social novelty and may represent a potential target for treating social disorders.
