Experience and activity refine cortical circuits through synapse elimination, but little is known about the activity patterns and downstream molecular mechanisms that mediate this process. We used optogenetics to drive individual mouse CA1 hippocampal neurons to fire in theta frequency bursts to understand how cell autonomous, postsynaptic activity leads to synapse elimination. Brief (1 hr) periods of postsynaptic bursting selectively depressed AMPA receptor (R) synaptic transmission, or silenced excitatory synapses, whereas more prolonged (24 hr) firing depressed both AMPAR and NMDAR EPSCs and eliminated spines, indicative of a synapse elimination. Both synapse silencing and elimination required de novo transcription, but only silencing required the activity-dependent transcription factors MEF2A/D. Burst firing induced MEF2A/D-dependent induction of the target gene Arc which contributed to synapse silencing and elimination. This work reveals new and distinct forms of activity and transcription-dependent synapse depression and suggests that these processes can occur independently.

中文翻译：

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突触消除的不同阶段是由 CA1 神经元的突发放电引起的，并且不同地需要 MEF2A/D

经验和活动通过突触消除来完善皮层回路，但对介导这一过程的活动模式和下游分子机制知之甚少。我们使用光遗传学来驱动单个小鼠 CA1 海马神经元在 theta 频率爆发中发射，以了解细胞自主性、突触后活动如何导致突触消除。短暂（1 小时）的突触后爆发选择性抑制了 AMPA 受体 (R) 突触传递，或抑制了兴奋性突触，而更长时间（24 小时）的发射抑制了 AMPAR 和 NMDAR EPSCs 并消除了棘突，表明突触消除。突触沉默和消除都需要从头转录，但只有沉默需要活性依赖性转录因子 MEF2A/D。突发放电诱导靶基因 Arc 的 MEF2A/D 依赖性诱导，这有助于突触沉默和消除。这项工作揭示了新的不同形式的活动和转录依赖性突触抑制，并表明这些过程可以独立发生。