Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA.
Nat Commun. 2023 Sep 29;14(1):6100. doi: 10.1038/s41467-023-41715-7.
Memory consolidation involves discrete patterns of transcriptional events in the hippocampus. Despite the emergence of single-cell transcriptomic profiling techniques, mapping the transcriptomic signature across subregions of the hippocampus has remained challenging. Here, we utilized unbiased spatial sequencing to delineate transcriptome-wide gene expression changes across subregions of the dorsal hippocampus of male mice following learning. We find that each subregion of the hippocampus exhibits distinct yet overlapping transcriptomic signatures. The CA1 region exhibited increased expression of genes related to transcriptional regulation, while the DG showed upregulation of genes associated with protein folding. Importantly, our approach enabled us to define the transcriptomic signature of learning within two less-defined hippocampal subregions, CA1 stratum radiatum, and oriens. We demonstrated that CA1 subregion-specific expression of a transcription factor subfamily has a critical functional role in the consolidation of long-term memory. This work demonstrates the power of spatial molecular approaches to reveal simultaneous transcriptional events across the hippocampus during memory consolidation.
记忆巩固涉及海马体中离散的转录事件模式。尽管单细胞转录组分析技术已经出现,但映射海马体亚区的转录组特征仍然具有挑战性。在这里,我们利用无偏空间测序技术,描绘了雄性小鼠学习后,海马体背侧各亚区的全基因组基因表达变化图谱。我们发现,海马体的每个亚区都表现出独特但重叠的转录组特征。CA1 区域表现出与转录调控相关基因的表达增加,而 DG 则表现出与蛋白质折叠相关基因的上调。重要的是,我们的方法使我们能够定义两个定义不太明确的海马体亚区(CA1 放射状层和 CA1 扇区)和或iens 中学习的转录组特征。我们证明了转录因子亚家族在 CA1 亚区的特异性表达在长时记忆的巩固中具有关键的功能作用。这项工作展示了空间分子方法在记忆巩固过程中揭示海马体中同时发生的转录事件的强大功能。