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Heterosynaptic long-term depression mediated by ATP released from astrocytes

Authors

  • Jiadong Chen,

    1. Institute of Neuroscience and Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    2. Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
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    • Jiadong Chen and Zhibing Tan contributed equally to this work.

  • Zhibing Tan,

    1. Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
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    • Jiadong Chen and Zhibing Tan contributed equally to this work.

  • Li Zeng,

    1. Department of Neurology, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China
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  • Xiaoxing Zhang,

    1. Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
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  • You He,

    1. Institute of Neuroscience and Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Wei Gao,

    1. Institute of Neuroscience and Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Xiumei Wu,

    1. Institute of Neuroscience and Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Yuju Li,

    1. Institute of Neuroscience and Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Bitao Bu,

    1. Department of Neurology, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China
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  • Wei Wang,

    1. Department of Neurology, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China
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  • Shumin Duan

    Corresponding author
    1. Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
    • Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
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Abstract

Heterosynaptic long-term depression (hLTD) at untetanized synapses accompanying the induction of long-term potentiation (LTP) spatially sharpens the activity-induced synaptic potentiation; however, the underlying mechanism remains unclear. We found that hLTD in the hippocampal CA1 region is caused by stimulation-induced ATP release from astrocytes that suppresses transmitter release from untetanized synaptic terminals via activation of P2Y receptors. Selective stimulation of astrocytes expressing channelrhodopsin-2, a light-gated cation channel permeable to Ca2+, resulted in LTD of synapses on neighboring neurons. This synaptic modification required Ca2+ elevation in astrocytes and activation of P2Y receptors, but not N-methyl-D-aspartate receptors. Furthermore, blocking P2Y receptors or buffering astrocyte intracellular Ca2+ at a low level prevented hLTD without affecting LTP induced by SC stimulation. Thus, astrocyte activation is both necessary and sufficient for mediating hLTD accompanying LTP induction, strongly supporting the notion that astrocytes actively participate in activity-dependent synaptic plasticity of neural circuits. © 2012 Wiley Periodicals, Inc.

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