Emotional memory processing engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network are unclear. Here, we illustrate that synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Transcriptome analyses revealed that PC-specific STAT3 knockout (STAT3PKO) results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber (PF) to PC synapses was larger in STAT3PKO mice than in wild-type (WT) littermates. Fear conditioning induced long-term depression of PF-PC synapses in STAT3PKO mice while the same manipulation induced long-term potentiation in WT littermates. STAT3PKO mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3PKO mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory.

中文翻译：

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浦肯野细胞中 STAT3 的消融重组了长期恐惧记忆网络中的小脑突触可塑性

情绪记忆处理涉及包括小脑在内的大脑区域的大型神经元网络。然而，小脑皮层调节恐惧记忆网络的分子和细胞机制尚不清楚。在这里，我们说明通过 STAT3 小脑浦肯野细胞 (PC) 中的突触信号调节长期恐惧记忆。转录组分析显示，PC 特异性 STAT3 敲除 (STAT3PKO) 会导致转录变化，从而导致谷氨酸受体表达增加。在 STAT3PKO 小鼠中，AMPA 受体介导的兴奋性突触后电流在平行纤维 (PF) 到 PC 突触的幅度大于野生型 (WT) 同窝小鼠。恐惧条件反射会导致 STAT3PKO 小鼠的 PF-PC 突触长期抑制，而相同的操作会导致 WT 同窝小鼠的长期增强。STAT3PKO 小鼠表现出异常增强的长期恐惧记忆。在恐惧条件下的 STAT3PKO 小鼠中，恐惧相关区域的神经元活动增加。我们的数据表明，PC 中依赖于 STAT3 的分子调控对于正确表达恐惧记忆是必不可少的。