Astrocytic Neuroligin 3 Regulates Social Memory and Synaptic Plasticity through Adenosine Signaling
Research Square (Research Square)(2023)
摘要
Abstract Social memory impairment is a key symptom of many brain disorders, but its underlying mechanisms remain unclear. Neuroligins (NLGs) are a family of cell adhesion molecules essential for synapse development and function and their dysfunctions are linked to neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. Although NLGs are extensively studied in neurons, their role in glial cells is poorly understood. Here we report that astrocytic NLG3 in the adult brain regulates social memory and synaptic plasticity through regulating glutamate homeostasis and adenosine signaling pathway. We show that astrocytic deletion of NLG3 in the ventral hippocampus impairs social recognition memory, attenuates experience-dependent astrocytic Ca 2+ signals, enhances the expression of glutamate transporter EAAT2 and prevents long-term potentiation, and these impairments are rescued by increasing astrocyte activity, reducing glutamate transporter function or enhancing adenosine/A2a receptor function. This study has revealed the critical roles of NLG3 in astrocyte function, glutamate homeostasis and social memory and identified the glutamate transporter and adenosine signaling pathway as potential therapeutic strategies to treat brain disorders.
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关键词
synaptic plasticity,social memory,adenosine signaling
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