Department of Biology, Pennsylvania State University, University Park, Pennsylvania, USA.
Nat Neurosci. 2010 Feb;13(2):223-31. doi: 10.1038/nn.2474. Epub 2009 Dec 27.
Changes in emotional state are known to alter neuronal excitability and can modify learning and memory formation. Such experience-dependent neuronal plasticity can be long-lasting and is thought to involve the regulation of gene transcription. We found that a single fear-inducing stimulus increased GluR2 (also known as Gria2) mRNA abundance and promoted synaptic incorporation of GluR2-containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch in synaptic AMPAR phenotype was mediated by noradrenaline and action potential prolongation. The subsequent rise in intracellular Ca(2+) and activation of Ca(2+)-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable receptors to GluR2-containing, Ca(2+)-impermeable receptors on the order of hours. The change in glutamate receptor phenotype altered synaptic efficacy in cerebellar stellate cells. Thus, a single fear-inducing stimulus can induce a long-term change in synaptic receptor phenotype and may alter the activity of an inhibitory neural network.
情绪状态的改变已知会改变神经元的兴奋性,并可以改变学习和记忆的形成。这种依赖经验的神经元可塑性可以是持久的,据认为涉及基因转录的调节。我们发现,单一的恐惧诱导刺激会增加GluR2(也称为 Gria2)mRNA 的丰度,并促进小鼠小脑星状细胞中含 GluR2 的 AMPA 受体(AMPAR)的突触整合。突触 AMPAR 表型的转变是由去甲肾上腺素和动作电位延长介导的。随后细胞内 Ca(2+)的增加和 Ca(2+)敏感的 ERK/MAPK 信号的激活触发了新的 GluR2 基因转录和突触 AMPAR 表型的转变,从 GluR2 缺失、Ca(2+)通透的受体转变为 GluR2 包含、Ca(2+)不透的受体,时间在数小时内。谷氨酸受体表型的变化改变了小脑星状细胞的突触效能。因此,单一的恐惧诱导刺激可以诱导突触受体表型的长期变化,并可能改变抑制性神经网络的活性。
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