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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function to coordinate adaptation to synaptic inactivity
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Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function to coordinate adaptation to synaptic inactivity

机译：突触后GluA1可使突触前功能急剧逆行增强，以协调对突触无活性的适应

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摘要

Prolonged blockade of AMPA-type glutamate receptors in hippo-campal neuron cultures leads to homeostatic enhancements of pre-and postsynaptic function that appear correlated at individual synapses, suggesting some form of transsynaptic coordination. The respective modifications are important for overall synaptic strength but their interrelationship, dynamics, and molecular underpinnings are unclear. Here we demonstrate that adaptation begins post-synaptically but is ultimately communicated to presynaptic terminals and expressed as an accelerated turnover of synaptic vesicles. Critical postsynaptic modifications occur over hours, but enable retrograde communication within minutes once AMPA receptor (AMPAR) blockade is removed, causing elevation of both spontaneous and evoked vesicle fusion. The retrograde signaling does not require spiking activity and can be interrupted by NBQX, philanthotoxin, postsynaptic BAPTA, or external sequestration of BDNF, consistent with the acute release of retrograde messenger, triggered by postsynaptic Ca~(2+) elevation via Ca~(2+)-permeable AMPARs.
机译：在海马-海马神经元培养物中对AMPA型谷氨酸受体的长期阻断导致突触前和突触后功能的稳态增强，这些功能在单个突触中似乎相关，表明某种形式的突触协调。各自的修饰对于总体突触强度很重要，但它们之间的相互关系，动力学和分子基础尚不清楚。在这里，我们证明了适应过程从突触后开始，但最终传达给突触前末端，并表示为突触小泡的加速周转。关键的突触后修饰会在数小时内发生，但一旦AMPA受体（AMPAR）阻滞被消除，则会在数分钟之内实现逆行通讯，从而导致自发和诱发的囊泡融合升高。逆行信号不需要刺突活动，并且可以被NBQX，philanthotoxin，突触后BAPTA或BDNF外部隔离所中断，这与由Ca〜（2）引起的突触后Ca〜（2+）升高触发的逆行信使的急性释放相一致。 +）可渗透的AMPAR。

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  • 作者

    Maria Lindskog; Li Li; Rachel D. Groth; Damon Poburko; Tara C. Thiagarajan; Xue Han; Richard W. Tsien;

  • 作者单位

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    homeostasis; synaptic scaling; calcium signaling; miniature excitatory postsynaptic currents;

    机译：稳态;突触缩放;钙信号;微型兴奋性突触后电流;

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