Vanrobeys Yann, Mukherjee Utsav, Langmack Lucy, Bahl Ethan, Lin Li-Chun, Michaelson Jacob J, Abel Ted, Chatterjee Snehajyoti
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.
bioRxiv. 2023 Jan 19:2023.01.18.524576. doi: 10.1101/2023.01.18.524576.
Memory consolidation involves discrete patterns of transcriptional events in the hippocampus. Despite the emergence of single-cell transcriptomic profiling techniques, defining learning-responsive gene expression across subregions of the hippocampus has remained challenging. Here, we utilized unbiased spatial sequencing to elucidate transcriptome-wide changes in gene expression in the hippocampus following learning, enabling us to define molecular signatures unique to each hippocampal subregion. We find that each subregion of the hippocampus exhibits distinct yet overlapping transcriptomic signatures. Although the CA1 region exhibited increased expression of genes related to transcriptional regulation, the DG showed upregulation of genes associated with protein folding. We demonstrate the functional relevance of subregion-specific gene expression by genetic manipulation of a transcription factor selectively in the CA1 hippocampal subregion, leading to long-term memory deficits. This work demonstrates the power of using spatial molecular approaches to reveal transcriptional events 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，但确定海马体各亚区域中学习反应性基因表达仍然具有挑战性。在这里，我们利用无偏空间测序来阐明学习后海马体中基因表达的全转录组变化，使我们能够定义每个海马体亚区域独特的分子特征。我们发现海马体的每个亚区域都表现出独特但重叠的转录组特征。虽然CA1区域表现出与转录调控相关基因的表达增加，但齿状回（DG）显示出与蛋白质折叠相关基因的上调。我们通过在CA1海马体亚区域选择性地对一种转录因子进行基因操作，证明了亚区域特异性基因表达的功能相关性，从而导致长期记忆缺陷。这项工作证明了使用空间分子方法揭示记忆巩固过程中转录事件的强大作用。
