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主动位置回避记忆中海马亚区和表达神经元群的空间分辨转录组特征

Spatially Resolved Transcriptomic Signatures of Hippocampal Subregions and -Expressing Ensembles in Active Place Avoidance Memory.

作者信息

Vingan Isaac, Phatarpekar Shwetha, Tung Victoria Sook Keng, Hernández A Iván, Evgrafov Oleg V, Alarcon Juan Marcos

机构信息

School of Graduates Studies, Program in Neural and Behavioral Sciences, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA.

Institute of Genomics in Health, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA.

出版信息

bioRxiv. 2024 Feb 16:2023.12.30.573225. doi: 10.1101/2023.12.30.573225.

Abstract

The rodent hippocampus is a spatially organized neuronal network that supports the formation of spatial and episodic memories. We conducted bulk RNA sequencing and spatial transcriptomics experiments to measure gene expression changes in the dorsal hippocampus following the recall of active place avoidance (APA) memory. Through bulk RNA sequencing, we examined the gene expression changes following memory recall across the functionally distinct subregions of the dorsal hippocampus. We found that recall induced differentially expressed genes (DEGs) in the CA1 and CA3 hippocampal subregions were enriched with genes involved in synaptic transmission and synaptic plasticity, while DEGs in the dentate gyrus (DG) were enriched with genes involved in energy balance and ribosomal function. Through spatial transcriptomics, we examined gene expression changes following memory recall across an array of spots encompassing putative memory-associated neuronal ensembles marked by the expression of the IEGs , , and . Within samples from both trained and untrained mice, the subpopulations of spatial transcriptomic spots marked by these IEGs were transcriptomically and spatially distinct from one another. DEGs detected between + and - spots exclusively in the trained mouse were enriched in several memory-related gene ontology terms, including "regulation of synaptic plasticity" and "memory." Our results suggest that APA memory recall is supported by regionalized transcriptomic profiles separating the CA1 and CA3 from the DG, transcriptionally and spatially distinct IEG expressing spatial transcriptomic spots, and biological processes related to synaptic plasticity as a defining the difference between + and - spatial transcriptomic spots.

摘要

啮齿动物海马体是一个空间组织化的神经元网络,支持空间记忆和情景记忆的形成。我们进行了大量RNA测序和空间转录组学实验,以测量主动位置回避(APA)记忆回忆后背侧海马体中的基因表达变化。通过大量RNA测序,我们研究了背侧海马体功能不同的亚区域在记忆回忆后的基因表达变化。我们发现,在海马体CA1和CA3亚区域中,回忆诱导的差异表达基因(DEGs)富含参与突触传递和突触可塑性的基因,而齿状回(DG)中的DEGs则富含参与能量平衡和核糖体功能的基因。通过空间转录组学,我们研究了在一系列包含由即刻早期基因(IEGs)、和的表达标记的假定记忆相关神经元集群的点上,记忆回忆后的基因表达变化。在训练和未训练小鼠的样本中,由这些IEGs标记的空间转录组学点亚群在转录和空间上彼此不同。仅在训练小鼠中在+和-点之间检测到的DEGs在几个与记忆相关的基因本体术语中富集,包括“突触可塑性调节”和“记忆”。我们的结果表明,APA记忆回忆由将CA1和CA3与DG分开的区域化转录组图谱、转录和空间上不同的表达IEG的空间转录组学点以及与突触可塑性相关的生物学过程支持作为定义+和-空间转录组学点之间差异的因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1efd/10878616/225d1f442c6a/nihpp-2023.12.30.573225v2-f0001.jpg

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