GPR158 in pyramidal neurons mediates social novelty behavior via modulating synaptic transmission in male mice
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.
Authors
- Jinlong Chang (ORCID: https://orcid.org/0000-0001-9831-8137)
- Shoupeng Wei (ORCID: https://orcid.org/0000-0002-0453-5008)
- Yiming Li (ORCID: https://orcid.org/0000-0003-4109-3824)
- Xiao-Ru Ma (ORCID: https://orcid.org/0000-0001-5337-7272)
- Dilong Wang
- Shuwen Chang
- Xinjin Chi (ORCID: https://orcid.org/0000-0001-8215-3235)
- Yu Zhao (ORCID: https://orcid.org/0000-0001-9025-2014)
- Ningning Li (ORCID: https://orcid.org/0000-0002-0414-5878)
- Xiuyan Yang (ORCID: https://orcid.org/0009-0003-8186-650X)
- Huiliang Li (ORCID: https://orcid.org/0000-0002-8274-3785)
- Jian Jiang (ORCID: https://orcid.org/0000-0002-5994-292X)
- Liusuyan Tian
Institutions
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Sir Run Run Shaw Hospital (CN)
- Southern University of Science and Technology (CN)
- The Seventh Affiliated Hospital of Sun Yat-sen University (CN)
- HKUST Shenzhen Research Institute (CN)
- Frontier Agriculture (United Kingdom) (GB)
- Shenzhen Institute of Neuroscience (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- University College London (GB)
- Zhejiang University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114796
- Citations
- 8
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 1.87