Lrp4 in astrocytes modulates glutamatergic transmission

Xiang Dong Sun, Lei Li, Fang Liu, Zhi Hui Huang, Jonathan C. Bean, Hui Feng Jiao, Arnab Barik, Seon Myung Kim, Haitao Wu, Chengyong Shen, Yun Tian, Thiri W. Lin, Ryan Bates, Anupama Sathyamurthy, Yong Jun Chen, Dong Min Yin, Lei Xiong, Hui Ping Lin, Jin Xia Hu, Bao Ming LiTian Ming Gao, Wen Cheng Xiong, Lin Mei

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Neurotransmission requires precise control of neurotransmitter release from axon terminals. This process is regulated by glial cells; however, the underlying mechanisms are not fully understood. We found that glutamate release in the brain was impaired in mice lacking low-density lipoprotein receptor-related protein 4 (Lrp4), a protein that is critical for neuromuscular junction formation. Electrophysiological studies revealed compromised release probability in astrocyte-specific Lrp4 knockout mice. Lrp4 mutant astrocytes suppressed glutamatergic transmission by enhancing the release of ATP, whose level was elevated in the hippocampus of Lrp4 mutant mice. Consequently, the mutant mice were impaired in locomotor activity and spatial memory and were resistant to seizure induction. These impairments could be ameliorated by blocking the adenosine A1 receptor. The results reveal a critical role for Lrp4, in response to agrin, in modulating astrocytic ATP release and synaptic transmission. Our findings provide insight into the interaction between neurons and astrocytes for synaptic homeostasis and/or plasticity.

Original languageEnglish (US)
Pages (from-to)1010-1018
Number of pages9
JournalNature Neuroscience
Issue number8
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • General Neuroscience


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