Mir125b-2 imprinted in human but not mouse brain regulates hippocampal function and circuit in mice

Ming Yi Chou, Xuhui Cao, Kuan Chu Hou, Meng Han Tsai, Chih Yu Lee, Meng Fai Kuo, Vin Cent Wu, Hsin Yi Huang, Schahram Akbarian, Sheng Kai Chang, Chung Yi Hu, Shu Wha Lin, Hsien Sung Huang

Research output: Contribution to journalArticlepeer-review


Genomic imprinting predominantly occurs in the placenta and brain. Few imprinted microRNAs have been identified in the brain, and their functional roles in the brain are not clear. Here we show paternal, but not maternal, expression of MIR125B2 in human but not mouse brain. Moreover, Mir125b-2m/p mice showed impaired learning and memory, and anxiety, whose functions were hippocampus-dependent. Hippocampal granule cells from Mir125b-2m/p mice displayed increased neuronal excitability, increased excitatory synaptic transmission, and decreased inhibitory synaptic transmission. Glutamate ionotropic receptor NMDA type subunit 2A (Grin2a), a key regulator of synaptic plasticity, was physically bound by miR-125b-2 and upregulated in the hippocampus of Mir125b-2m/p mice. Taken together, our findings demonstrate MIR125B2 imprinted in human but not mouse brain, mediated learning, memory, and anxiety, regulated excitability and synaptic transmission in hippocampal granule cells, and affected hippocampal expression of Grin2a. Our work provides functional mechanisms of a species-specific imprinted microRNA in the brain.

Original languageEnglish
Article number267
JournalCommunications Biology
Issue number1
StatePublished - Dec 2023


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