Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation.

中文翻译：

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Npas4是在上下文记忆形成过程中长满苔藓的纤维-CA3突触学习诱导可塑性的关键调节器。

海马苔藓纤维（MF）和CA3锥体神经元之间的突触连接对于上下文记忆编码是必不可少的，但是在记忆形成过程中调节MF-CA3突触的分子机制以及这种调节的确切性质尚不清楚。在这里，我们报告活动依赖转录因子Npas4通过限制其功能性突触接触的数量而不影响到CA3锥体神经元的其他突触输入，选择性地调节MF-CA3突触的结构和强度。使用活动依赖的记者，我们确定了由上下文学习激活的CA3锥体细胞，并发现选择性增强了这些细胞上的MF输入。Npas4的删除阻止了上下文记忆的形成和这种学习引起的突触修饰。我们进一步表明，Npas4通过控制polo样激酶Plk2的表达来调节MF-CA3突触。因此，Npas4是上下文记忆形成过程中MF-CA3突触处经验依赖，结构和功能可塑性的关键调节器。