Activity bidirectionally regulates AMPA receptor mRNA abundance in dendrites of hippocampal neurons
Activity bidirectionally regulates AMPA receptor mRNA abundance in dendrites of hippocampal neurons
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DOI：
10.1523/jneurosci.0472-06.2006
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发表时间：
2006-08-09
影响因子：
5.3
通讯作者：
Zukin, R. Suzanne
中科院分区：
文献类型：
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作者：
Grooms, Sonja Y.;Noh, Kyung-Min;Zukin, R. Suzanne
突触AMPA受体(AMPAR)数量的活性依赖调节对NMDAR依赖的突触可塑性至关重要。利用定量高分辨率原位杂交，我们发现编码AMPA型谷氨酸受体亚单位(GluRs)1和2的mRNAs定位于海马神经元的树突，并受到改变突触效力的范例的调节。相当一部分突触部位含有AMPAR mRNA，这与“现场”蛋白质合成的战略定位和可用性是一致的。NMDAR的激活耗尽了AMPAR mRNAs的树突状水平。MRNA的减少是通过细胞内钙离子的升高，激活细胞外信号调节的激酶/有丝分裂原激活的蛋白激酶信号，以及在细胞核水平上的转录抑制而发生的。MRNA的减少伴随着突触AMPAR数量的长期减少，这与突触效能的降低是一致的。相反，I组代谢性GluR信号促进现有AMPAR mRNAs从胞体到树突的基于微管的运输。双向调节树突状细胞的mRNA丰度是影响突触强度长期变化的一种潜在的有效手段。
Activity-dependent regulation of synaptic AMPA receptor (AMPAR) number is critical toNMDAreceptor (NMDAR)-dependent synaptic plasticity. Using quantitative high-resolution in situ hybridization, we show that mRNAs encoding the AMPA-type glutamate receptor subunits (GluRs) 1 and 2 are localized to dendrites of hippocampal neurons and are regulated by paradigms that alter synaptic efficacy. A substantial fraction of synaptic sites contain AMPAR mRNA, consistent with strategic positioning and availability for "on-site" protein synthesis. NMDAR activation depletes dendritic levels of AMPAR mRNAs. The decrease in mRNA occurs via rise in intracellular Ca2+, activation of extracellular signal-regulated kinase/mitogen-activated protein kinase signaling, and transcriptional arrest at the level of the nucleus. The decrease in mRNA is accompanied by a long-lasting reduction in synaptic AMPAR number, consistent with reduced synaptic efficacy. In contrast, group I metabotropic GluR signaling promotes microtubule-based trafficking of existing AMPAR mRNAs from the soma to dendrites. Bidirectional regulation of dendritic mRNA abundance represents a potentially powerful means to effect long-lasting changes in synaptic strength.