Astrocytic neuroligin 3 regulates social memory and synaptic plasticity through adenosine signaling in male mice

Social memory impairment is a key symptom of many brain disorders. Neuroligins (NLGs) are cell adhesion molecules essential for synapse development and function, and their dysfunctions are linked to neurodevelopmental and neuropsychiatric disorders. This study shows that astrocytic deletion of NLG3 in the ventral hippocampus of adult male mice impairs social memory, attenuates astrocytic Ca2+ signals, enhances EAAT2 expression, and prevents long-term potentiation (LTP). These impairments are rescued by increasing astrocyte activity, reducing EAAT2 function, or enhancing adenosine/A2a receptor signaling. The study reveals an important role of NLG3 in astrocyte function, glutamate homeostasis, and social memory, identifying the glutamate transporter and adenosine signaling pathway as potential therapeutic strategies.

Rui Dang, An Liu, Yu Zhou, Xingcan Li, Miao Wu, Kun Cao, Yanghong Meng, Haiwang Zhang, Guangming Gan, Wei Xie, Zhengping Jia