Suppr超能文献

由胶质细胞肿瘤坏死因子-α介导的突触缩放。

Synaptic scaling mediated by glial TNF-alpha.

作者信息

Stellwagen David, Malenka Robert C

机构信息

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

出版信息

Nature. 2006 Apr 20;440(7087):1054-9. doi: 10.1038/nature04671. Epub 2006 Mar 19.

Abstract

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.

摘要

在发育过程中,两种作用于不同时间尺度的突触可塑性一般形式被认为有助于神经回路的活动依赖性精细化:(1)长时程增强(LTP)和长时程抑制(LTD),它们涉及单个突触强度根据相关突触活动的特定模式进行快速调整;(2)稳态突触缩放,它需要细胞上所有突触的强度根据细胞电活动的长期变化进行统一调整。没有稳态突触缩放,神经网络可能会变得不稳定且表现欠佳。尽管关于LTP和LTD的潜在机制已了解很多,但对于负责突触缩放的机制却知之甚少,只知道这种缩放至少部分归因于突触处受体含量的改变。在这里,我们表明,对活动的长期阻断作出反应的突触缩放是由促炎细胞因子肿瘤坏死因子-α(TNF-α)介导的。使用野生型和TNF-α缺陷型神经元及神经胶质细胞的混合物,我们还表明,神经胶质细胞是这种形式的突触缩放所需的TNF-α的来源。我们认为,通过调节TNF-α水平,神经胶质细胞积极参与突触连接的稳态活动依赖性调节。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验