Microglia modulate memories Synaptic reorganization and circuit rewiring leads to loss or weakening of connections between neurons and may result in the erasure of previously formed memories. Microglia eliminate excessive synapses in the developing brain and regulate the dynamics of synaptic connections between neurons throughout life. However, it is still unclear whether forgetting is related to microglia activity and how microglia regulate memory erasure in the adult brain. Wang et al. discovered that microglia eliminated synaptic components in the adult hippocampus and that depleting microglia or inhibiting phagocytosis of microglia prevented forgetting. Synapse elimination by microglia may thus lead to degradation of memory engrams and forgetting of previously learned contextual fear memory. Science, this issue p. 688 Elimination of synapses in the mouse brain by microglia mediates dissociation of engram cells and forgetting of previously learned memories. Synapses between engram cells are believed to be substrates for memory storage, and the weakening or loss of these synapses leads to the forgetting of related memories. We found engulfment of synaptic components by microglia in the hippocampi of healthy adult mice. Depletion of microglia or inhibition of microglial phagocytosis prevented forgetting and the dissociation of engram cells. By introducing CD55 to inhibit complement pathways, specifically in engram cells, we further demonstrated that microglia regulated forgetting in a complement- and activity-dependent manner. Additionally, microglia were involved in both neurogenesis-related and neurogenesis-unrelated memory degradation. Together, our findings revealed complement-dependent synapse elimination by microglia as a mechanism underlying the forgetting of remote memories.

中文翻译：

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小胶质细胞通过依赖补体的突触消除介导遗忘

小胶质细胞调节记忆突触重组和电路重新布线导致神经元之间的连接丢失或减弱，并可能导致先前形成的记忆的擦除。小胶质细胞消除发育中大脑中过多的突触，并在整个生命过程中调节神经元之间突触连接的动态。然而，尚不清楚遗忘是否与小胶质细胞活动有关，以及小胶质细胞如何调节成人大脑中的记忆擦除。王等人。发现小胶质细胞消除了成年海马中的突触成分，消耗小胶质细胞或抑制小胶质细胞的吞噬作用可以防止遗忘。因此，小胶质细胞对突触的消除可能导致记忆印迹的退化和忘记先前学习的情境恐惧记忆。科学，这个问题 p。688 小胶质细胞对小鼠大脑中突触的消除介导了印迹细胞的分离和对先前学习记忆的遗忘。印迹细胞之间的突触被认为是记忆存储的底物，这些突触的减弱或丧失会导致相关记忆的遗忘。我们发现健康成年小鼠海马中的小胶质细胞吞噬了突触成分。小胶质细胞的消耗或小胶质细胞吞噬作用的抑制可防止遗忘和印迹细胞的分离。通过引入 CD55 来抑制补体通路，特别是在印迹细胞中，我们进一步证明小胶质细胞以补体和活性依赖的方式调节遗忘。此外，小胶质细胞参与了神经发生相关和神经发生无关的记忆退化。一起，