Histone Lysine Crotonylation Regulates Long-Term Memory Storage

Utilizing a single nuclei multiomics approach, this study elucidates how enhancing histone lysine crotonylation regulates cell type specific gene expression and chromatin accessibility during memory consolidation. To study the impact of crotonate administration on memory enhancement, mice were trained in Spatial Object Recognition (SOR) task using a sub-threshold learning paradigm, and oral administration of crotonate (200 mg/kg) or vehicle (Saline) was given immediately after the completion of the training trials. 1hr after crotonate administration, the dorsal hippocampus was harvested, and nuclei were isolated for single nuclei multiomics. We performed multiomic sequencing (snRNA-seq + snATAC-seq) obtained from the dorsal hippocampus of 2 groups (Crotonate1+Crotonate2 vs. Saline1+Saline2).本研究借助单细胞核多组学（single nuclei multiomics）技术，阐明了记忆巩固过程中，增强组蛋白赖氨酸巴豆酰化（histone lysine crotonylation）如何调控细胞类型特异性基因表达与染色质可及性。为探究巴豆酸盐给药对记忆增强的作用，本研究采用亚阈值学习范式对小鼠实施空间物体识别（Spatial Object Recognition, SOR）任务训练，并于训练结束后即刻对小鼠口服给予200 mg/kg的巴豆酸盐或溶媒（生理盐水）。巴豆酸盐给药1小时后，采集小鼠背侧海马组织并分离细胞核，用于单细胞核多组学研究。本研究对两组小鼠（Crotonate1+Crotonate2 与 Saline1+Saline2）的背侧海马组织开展了多组学测序，即联用单细胞核RNA测序（snRNA-seq）与单细胞核转座酶可及性测序（snATAC-seq）。