Single-nucleus RNA sequencing-based construction of a hippocampal neuron atlas in mice with epileptic cognitive impairment.

The hippocampus plays a critical role in learning and memory, and mice with epileptic cognitive impairment exhibit hippocampal atrophy. However, there is still a lack of research on the hippocampal cell atlas related to these disorders. Here, we utilized snRNA-seq to characterize the transcriptomic changes in hippocampal neurons of drug-resistant epilepsy (DRE) cognitive-impaired mice. The intercellular heterogeneity of 20 subpopulations of neurons was analyzed, focusing on aspects such as cell communication, gene expressions, GO and KEGG enrichment analysis, and module gene set analysis. Based on the degree of relevance to synaptic biological functions, the subpopulations associated with cognitive impairment (ExN1, 3, 8 and InN1, 6) were preliminarily identified. We also identified some key biomarkers in DRE cognitive-impaired mice, such as Ptprz1 and Calb1. Finally, we integrate and validate our dataset using identified well-annotated marker genes in the hippocampal region, further supporting the functional annotation of neuronal subpopulations.