In the adult hippocampus, synapses are constantly formed and eliminated1,2. However, the exact function of synapse elimination in the adult brain, and how it is regulated, are largely unknown. Here we show that astrocytic phagocytosis3 is important for maintaining proper hippocampal synaptic connectivity and plasticity. By using fluorescent phagocytosis reporters, we find that excitatory and inhibitory synapses are eliminated by glial phagocytosis in the CA1 region of the adult mouse hippocampus. Unexpectedly, we found that astrocytes have a major role in the neuronal activity-dependent elimination of excitatory synapses. Furthermore, mice in which astrocytes lack the phagocytic receptor MEGF10 show a reduction in the elimination of excitatory synapses; as a result, excessive but functionally impaired synapses accumulate. Finally, Megf10-knockout mice show defective long-term synaptic plasticity and impaired formation of hippocampal memories. Together, our data provide strong evidence that astrocytes eliminate unnecessary excitatory synaptic connections in the adult hippocampus through MEGF10, and that this astrocytic function is crucial for maintaining circuit connectivity and thereby supporting cognitive function.

中文翻译：

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星形胶质细胞吞噬成人海马突触以实现回路稳态

在成年海马体中，突触不断地形成和消除1,2。然而，成人大脑中突触消除的确切功能及其调节方式在很大程度上是未知的。在这里，我们表明星形胶质细胞吞噬作用3对于维持适当的海马突触连接和可塑性很重要。通过使用荧光吞噬记者，我们发现兴奋性和抑制性突触被成年小鼠海马 CA1 区域的神经胶质吞噬作用消除。出乎意料的是，我们发现星形胶质细胞在兴奋性突触的神经元活动依赖性消除中起主要作用。此外，星形胶质细胞缺乏吞噬受体 MEGF10 的小鼠表现出兴奋性突触的消除减少；结果，过度但功能受损的突触积累。最后，Megf10 基因敲除小鼠表现出有缺陷的长期突触可塑性和受损的海马记忆形成。总之，我们的数据提供了强有力的证据，表明星形胶质细胞通过 MEGF10 消除了成年海马中不必要的兴奋性突触连接，并且这种星形胶质细胞功能对于维持电路连接并从而支持认知功能至关重要。