Astrocytes play a critical role in synapse elimination through the MEGF10 and MERTK pathways in both developing and adult brains. This study demonstrates that astrocytes actively engulf synapses, a process that is essential for neural circuit refinement. The MEGF10 and MERTK pathways are involved in recognizing "eat me" signals, such as phosphatidylserine, present on target debris, enabling astrocytes to mediate synapse elimination. In developing mice, astrocytes deficient in these pathways fail to refine retinogeniculate connections and retain excess synapses. In the adult brain, astrocytes continue to engulf both excitatory and inhibitory synapses, indicating a continuous role in synaptic remodeling. The study also shows that astrocytes and microglia both contribute to synapse elimination, but astrocytes are more abundant and play a significant role in synaptic pruning. The findings highlight the importance of astrocytes in neural circuit refinement and synaptic turnover, with implications for understanding learning, memory, and neurological diseases. The research provides new insights into the mechanisms underlying synapse elimination and the role of astrocytes in maintaining brain function.Astrocytes play a critical role in synapse elimination through the MEGF10 and MERTK pathways in both developing and adult brains. This study demonstrates that astrocytes actively engulf synapses, a process that is essential for neural circuit refinement. The MEGF10 and MERTK pathways are involved in recognizing "eat me" signals, such as phosphatidylserine, present on target debris, enabling astrocytes to mediate synapse elimination. In developing mice, astrocytes deficient in these pathways fail to refine retinogeniculate connections and retain excess synapses. In the adult brain, astrocytes continue to engulf both excitatory and inhibitory synapses, indicating a continuous role in synaptic remodeling. The study also shows that astrocytes and microglia both contribute to synapse elimination, but astrocytes are more abundant and play a significant role in synaptic pruning. The findings highlight the importance of astrocytes in neural circuit refinement and synaptic turnover, with implications for understanding learning, memory, and neurological diseases. The research provides new insights into the mechanisms underlying synapse elimination and the role of astrocytes in maintaining brain function.