TY  - JOUR
TI  - GPR158 in pyramidal neurons mediates social novelty behavior via modulating synaptic transmission in male mice
JF  - Cell Reports
N1  - © 2024 The Author(s). Published by Elsevier Inc. 
This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
UR  - https://doi.org/10.1016/j.celrep.2024.114796
Y1  - 2024/10/22/
N2  - 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.
PB  - Elsevier BV
A1  - Wei, Shoupeng
A1  - Jiang, Jian
A1  - Wang, Dilong
A1  - Chang, Jinlong
A1  - Tian, Liusuyan
A1  - Yang, Xiuyan
A1  - Ma, Xiao-Ru
A1  - Zhao, Jing-Wei
A1  - Li, Yiming
A1  - Chang, Shuwen
A1  - Chi, Xinjin
A1  - Li, Huiliang
A1  - Li, Ningning
SN  - 2211-1247
KW  - GPR158
KW  -  
social novelty
KW  -  
pyramidal neurons
KW  -  
synaptic transmission
KW  -  
medial prefrontal cortex
IS  - 10
VL  - 43
ID  - discovery10198309
AV  - public
ER  -