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Synaptic scaling mediated by glial TNF-alpha.

机译：由神经胶质TNF-α介导的突触缩放。

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摘要

Two general forms of synaptic plasticity that operate on different timescales are thought to contribute to the activity-dependent refinement of neural circuitry during development: (1) long-term potentiation (LTP) and long-term depression (LTD), which involve rapid adjustments in the strengths of individual synapses in response to specific patterns of correlated synaptic activity, and (2) homeostatic synaptic scaling, which entails uniform adjustments in the strength of all synapses on a cell in response to prolonged changes in the cell's electrical activity. Without homeostatic synaptic scaling, neural networks can become unstable and perform suboptimally. Although much is known about the mechanisms underlying LTP and LTD, little is known about the mechanisms responsible for synaptic scaling except that such scaling is due, at least in part, to alterations in receptor content at synapses. Here we show that synaptic scaling in response to prolonged blockade of activity is mediated by the pro-inflammatory cytokine tumour-necrosis factor-alpha (TNF-alpha). Using mixtures of wild-type and TNF-alpha-deficient neurons and glia, we also show that glia are the source of the TNF-alpha that is required for this form of synaptic scaling. We suggest that by modulating TNF-alpha levels, glia actively participate in the homeostatic activity-dependent regulation of synaptic connectivity.
机译：人们认为，在不同的时间尺度上起作用的两种一般形式的突触可塑性有助于发育过程中神经回路的活动依赖性细化：（1）长期增强（LTP）和长期抑郁（LTD），涉及快速调整（2）稳态突触缩放，这是对细胞中所有突触强度的统一调节，以响应细胞电活动的长期变化。如果没有稳态突触缩放，神经网络可能会变得不稳定并表现欠佳。尽管对LTP和LTD的潜在机制了解甚多，但对导致突触缩放的机制知之甚少，除了这种缩放至少部分是由于突触中受体含量的改变所致。在这里，我们表明响应于长时间的活动阻滞的突触缩放是由促炎性细胞因子肿瘤坏死因子-α（TNF-α）介导的。使用野生型和TNF-α缺陷型神经元和神经胶质的混合物，我们还显示神经胶质是这种形式的突触缩放所需的TNF-α的来源。我们建议通过调节TNF-α的水平，胶质细胞积极参与稳态活动依赖突触连接的调节。

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  • 来源
    《Nature》 |2006年第7087期|P.1054-1059|共6页
  • 作者

    Stellwagen D; Malenka RC;

  • 作者单位

    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California 94304-5485, USA.;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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
  • 中图分类 基础医学;
  • 关键词

    Neuroglia; Synapses; Tumor Necrosis Factor-alpha; 神经胶质; 突触;

    机译：Neuroglia;Synapses;Tumor Necrosis Factor-alpha;神经胶质;突触;

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