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 (1hr) 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-dependent synapse depression and suggests that these processes can occur independently.

经验和活性通过消除突触来改善皮层回路，但对介导该过程的活性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θ频率突发中激发，以了解细胞自主，突触后活性如何导致突触消除。短暂的（1小时）突触后爆发选择性抑制AMPA受体（R）突触传递或沉默的兴奋性突触，而更长的（24小时）发射会抑制AMPAR和NMDAR EPSC并消除棘突，这表明突触消除。从头开始需要突触沉默和消除转录，但只有沉默需要活性依赖的转录因子MEF2A / D。爆发射击诱导了目标基因Arc的MEF2A / D依赖性诱导，这有助于突触的沉默和消除。这项工作揭示了新的和不同形式的活动依赖性突触抑制，并建议这些过程可以独立发生。