Kdm3b haploinsufficiency impairs the consolidation of cerebellum-dependent motor memory in mice

Molecular Brain

Ye Lee Kim¹  Joon-Yong An²  Yujin Kim²  Sang-Beom Seo³  Yun-Cheol Chae³  Yong Gyu Kim⁴  Myeong Seong Bak⁴  Ahbin Kim⁴  Yang-Sook Chun⁵  Sang Jeong Kim⁶  Yong-Seok Lee⁶ 

[1] Department of Biomedical Sciences, Seoul National University College of Medicine, 03080, Seoul, Korea;Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 03080, Seoul, Korea;Department of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, 02841, Seoul, Korea;Department of Integrated Biomedical and Life Sciences, College of Health Sciences, Korea University, Seoul, Korea;Department of Life Science, College of Natural Science, Chung-Ang University, 06974, Seoul, Korea;Department of Physiology, Seoul National University College of Medicine, 03080, Seoul, Korea;Department of Biomedical Sciences, Seoul National University College of Medicine, 03080, Seoul, Korea;Department of Physiology, Seoul National University College of Medicine, 03080, Seoul, Korea;Department of Biomedical Sciences, Seoul National University College of Medicine, 03080, Seoul, Korea;Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 03080, Seoul, Korea;Department of Physiology, Seoul National University College of Medicine, 03080, Seoul, Korea;Department of Biomedical Sciences, Seoul National University College of Medicine, 03080, Seoul, Korea;Neuroscience Research Institute, Seoul National University College of Medicine, 03080, Seoul, Korea;

关键词: Kdm3b;    Optokinetic response (OKR);    Histone modification;    Cerebellum;   

DOI  :  10.1186/s13041-021-00815-5

来源: Springer

【 摘 要 】

Histone modifications are a key mechanism underlying the epigenetic regulation of gene expression, which is critically involved in the consolidation of multiple forms of memory. However, the roles of histone modifications in cerebellum-dependent motor learning and memory are not well understood. To test whether changes in histone methylation are involved in cerebellar learning, we used heterozygous Kdm3b knockout (Kdm3b+/−) mice, which show reduced lysine 9 on histone 3 (H3K9) demethylase activity. H3K9 di-methylation is significantly increased selectively in the granule cell layer of the cerebellum of Kdm3b+/− mice. In the cerebellum-dependent optokinetic response (OKR) learning, Kdm3b+/− mice show deficits in memory consolidation, whereas they are normal in basal oculomotor performance and OKR acquisition. In addition, RNA-seq analyses revealed that the expression levels of several plasticity-related genes were altered in the mutant cerebellum. Our study suggests that active regulation of histone methylation is critical for the consolidation of cerebellar motor memory.

【 授权许可】

CC BY