Long noncoding RNAs (lncRNAs) play crucial roles in maintaining cell homeostasis and function. However, it remains largely unknown whether and how neuronal activity impacts the transcriptional regulation of lncRNAs, or if this leads to synapse-related changes and contributes to the formation of long-term memories. Here, we report the identification of a lncRNA, SLAMR, which becomes enriched in CA1-hippocampal neurons upon contextual fear conditioning but not in CA3 neurons. SLAMR is transported along dendrites via the molecular motor KIF5C and is recruited to the synapse upon stimulation. Loss of function of SLAMR reduces dendritic complexity and impairs activity-dependent changes in spine structural plasticity and translation. Gain of function of SLAMR, in contrast, enhances dendritic complexity, spine density, and translation. Analyses of the SLAMR interactome reveal its association with CaMKIIα protein through a 220-nucleotide element also involved in SLAMR transport. A CaMKII reporter reveals a basal reduction in CaMKII activity with SLAMR loss-of-function. Furthermore, the selective loss of SLAMR function in CA1 disrupts the consolidation of fear memory in male mice, without affecting their acquisition, recall, or extinction, or spatial memory. Together, these results provide new molecular and functional insight into activity-dependent changes at the synapse and consolidation of contextual fear.

长非编码 RNA (lncRNA) 在维持细胞稳态和功能中发挥着至关重要的作用。然而，神经元活动是否以及如何影响 lncRNA 的转录调控，或者这是否会导致突触相关的变化并有助于长期记忆的形成，目前仍不清楚。在这里，我们报告了一种 lncRNA SLAMR 的鉴定，它在情境恐惧调节后在 CA1 海马神经元中富集，但在 CA3 神经元中却没有富集。 SLAMR 通过分子马达 KIF5C 沿着树突运输，并在受到刺激时被招募到突触。 SLAMR 功能的丧失会降低树突的复杂性，并损害脊柱结构可塑性和翻译的活动依赖性变化。相反，SLAMR 功能的增强增强了树突复杂性、树突棘密度和翻译能力。对 SLAMR 相互作用组的分析揭示了它通过也参与 SLAMR 转运的 220 个核苷酸元件与 CaMKIIα 蛋白的关联。 CaMKII 报告基因揭示了 CaMKII 活性的基础降低和 SLAMR 功能丧失。此外，CA1区SLAMR功能的选择性丧失会破坏雄性小鼠恐惧记忆的巩固，但不会影响它们的获得、回忆或消退或空间记忆。总之，这些结果为突触的活动依赖性变化和情境恐惧的巩固提供了新的分子和功能见解。