GPR50 regulates social memory formation

The ability to remember and recognize familiar conspecifics is essential for social interaction. Social memory disorders affect normal social interaction. Engram neurons relate to social memory formation with unclear mechanisms. G protein-coupled receptor 50 (GPR50) is an X chromosome-associated orphan receptor and is highly expressed in neurons. In this study, using social disorders mouse model establishing, chemical modulation, electrophysiology, and RNAseq, we herein report a novel role of GPR50 in social memory formation via activating engram neurons. Our results demonstrate that GPR50 upregulation in the excitatory neurons enhances cAMP/p-CREB signaling, which increases the excitability of hippocampal neurons, neuronal firing, and synaptic plasticity, eventually triggering social memory formation. Our study demonstrates a key role of GPR50 in regulating social memory formation.