Homeostatic scaling requires group I mGluR activation mediated by Homer1a.

Homeostatic scaling requires group I mGluR activation mediated by Homer1a.
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DOI:
10.1016/j.neuron.2010.11.008
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发表时间:
2010-12-22
期刊:
影响因子:
16.2
通讯作者:
Worley PF
Worley PF
中科院分区:
医学1区
文献类型:
--
作者:
Hu JH;Park JM;Park S;Xiao B;Dehoff MH;Kim S;Hayashi T;Schwarz MK;Huganir RL;Seeburg PH;Linden DJ;Worley PF

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稳态标度是一种非赫布形式的神经可塑性,它在网络活动变化时保持神经元的兴奋性和突触阵列的信息内容。在这里,我们证明,稳态缩放依赖于I组代谢型谷氨酸受体激活,是由即时早期基因Homer 1a介导的。Homer 1a在网络活动增加期间瞬时上调,并引起I组mGluRs的激动剂非依赖性信号传导,其按比例降低突触AMPA受体的表达。Homer 1a效应是动态的,并在结垢的诱导中发挥作用。与mGluR-LTD类似,Homer 1a依赖性缩放涉及GluA 2(GluR 2)酪氨酸磷酸化的减少,但不同之处在于它利用I组mGluR的独特信号传导特性来赋予受体的细胞范围的激动剂非依赖性激活。这些研究揭示了赫布和非赫布可塑性的基础机制的优雅的相互作用。
Homeostatic scaling is a non-Hebbian form of neural plasticity that maintains neuronal excitability and informational content of synaptic arrays in the face of changes of network activity. Here, we demonstrate that homeostatic scaling is dependent on group I metabotropic glutamate receptor activation that is mediated by the immediate early gene Homer1a. Homer1a is transiently up-regulated during increases in network activity and evokes agonist-independent signaling of group I mGluRs that scales down the expression of synaptic AMPA receptors. Homer1a effects are dynamic and play a role in the induction of scaling. Similar to mGluR-LTD, Homer1a-dependent scaling involves a reduction of tyrosine phosphorylation of GluA2 (GluR2), but is distinct in that it exploits a unique signaling property of group I mGluR to confer cell-wide, agonist-independent activation of the receptor. These studies reveal an elegant interplay of mechanisms that underlie Hebbian and non-Hebbian plasticity.
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