The ability of neurons to process and store salient environmental features underlies information processing in the brain. Long-term information storage requires synaptic plasticity and regulation of gene expression. While distinct patterns of activity have been linked to synaptic plasticity, their impact on immediate early gene (IEG) expression remains poorly understood. The activity regulated cytoskeleton associated ( Arc ) gene has received wide attention as an IEG critical for long-term synaptic plasticity and memory. Yet, to date, the transcriptional dynamics of Arc in response to compartment and input-specific activity is unclear. By developing a knock-in mouse to fluorescently tag Arc alleles, we studied real-time transcription dynamics after stimulation of dentate granule cells (GCs) in acute hippocampal slices. To our surprise, we found that Arc transcription displayed distinct temporal kinetics depending on the activation of excitatory inputs that convey functionally distinct information, i.e., medial and lateral perforant paths (MPP and LPP, respectively). Moreover, the transcriptional dynamics of Arc after synaptic stimulation was similar to direct activation of GCs, although the contribution of ionotropic glutamate receptors, L-type voltage-gated calcium channel, and the endoplasmic reticulum (ER) differed. Specifically, we observed an ER-mediated synapse-to-nucleus signal that supported elevations in nuclear calcium and, thereby, rapid induction of Arc transcription following MPP stimulation. By delving into the complex excitation–transcription coupling for Arc , our findings highlight how different synaptic inputs may encode information by modulating transcription dynamics of an IEG linked to learning and memory.

中文翻译：

---

Arc/Arg3.1 离体转录的实时成像揭示了输入特定的即时早期基因动力学

神经元处理和存储显着环境特征的能力是大脑信息处理的基础。长期信息存储需要突触可塑性和基因表达调控。虽然不同的活动模式与突触可塑性有关，但它们对即刻早期基因 (IEG) 表达的影响仍然知之甚少。活性调节细胞骨架相关（弧) 基因作为对长期突触可塑性和记忆至关重要的 IEG 受到广泛关注。然而，迄今为止，转录动力学弧对车厢和输入特定活动的反应尚不清楚。通过开发敲入小鼠来荧光标记弧等位基因，我们研究了在急性海马切片中刺激齿状颗粒细胞 (GC) 后的实时转录动力学。令我们惊讶的是，我们发现弧转录显示出不同的时间动力学，这取决于传递功能不同信息的兴奋性输入的激活，即内侧和外侧穿孔路径（分别为 MPP 和 LPP）。此外，转录动力学弧突触刺激后类似于 GCs 的直接激活，尽管离子型谷氨酸受体、L 型电压门控钙通道和内质网 (ER) 的贡献不同。具体而言，我们观察到 ER 介导的突触到细胞核信号，支持核钙升高，从而快速诱导弧MPP 刺激后的转录。通过深入研究复杂的激发-转录耦合弧，我们的研究结果强调了不同的突触输入如何通过调节与学习和记忆相关的 IEG 的转录动力学来编码信息。