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An activity-dependent determinant of synapse elimination in the mammalian brain

机译：哺乳动物脑中突触消除的活动依赖性决定因素

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摘要

To establish functional neural circuits in the brain, synaptic connections are refined by neural activity during development, where active connections are maintained and inactive ones are eliminated. However, the molecular signals that regulate synapse refinement remain to be elucidated. When we inactivate a subset of neurons in the mouse cingulate cortex, their callosal connections are eliminated through activity-dependent competition. Using this system, we identify JAK2 tyrosine kinase as a key regulator of inactive synapse elimination. We show that JAK2 is necessary and sufficient for elimination of inactive connections; JAK2 is activated at inactive synapses in response to signals from other active synapses; STAT1, a substrate of JAK2, mediates inactive synapse elimination; JAK2 signaling is critical for physiological refinement of synapses during normal development; and JAK2 regulates synapse refinement in multiple brain regions. We propose that JAK2 is an activity-dependent switch that serves as a determinant of inactive synapse elimination.
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  • 来源
    《Neuron》 |2021年第8期|共23页
  • 作者

    Yasuda Masahiro; Nagappan-Chettiar Sivapratha; Johnson-Venkatesh Erin M.; Umemori Hisashi;

  • 作者单位

    Harvard Med Sch FM Kirby Neurobiol Ctr Boston Childrens Hosp Dept Neurol Boston MA 02115 USA;

    Harvard Med Sch FM Kirby Neurobiol Ctr Boston Childrens Hosp Dept Neurol Boston MA 02115 USA;

    Harvard Med Sch FM Kirby Neurobiol Ctr Boston Childrens Hosp Dept Neurol Boston MA 02115 USA;

    Harvard Med Sch FM Kirby Neurobiol Ctr Boston Childrens Hosp Dept Neurol Boston MA 02115 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
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