Glutamate Receptor Modulation Is Restricted to Synaptic Microdomains.
Glutamate Receptor Modulation Is Restricted to Synaptic Microdomains.
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DOI：
10.1016/j.celrep.2015.06.029
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发表时间：
2015-07-14
期刊：
影响因子：
8.8
通讯作者：
Higley MJ
中科院分区：
文献类型：
--
作者：
Lur G;Higley MJ
一系列不同的神经调节剂通过激活G蛋白偶联受体(GPCRs)来调节前额叶皮质(PFC)的细胞功能。然而，这些功能不同的信号是由相对较少的细胞内第二信使携带和放大的。在这里，我们研究了两种不同的G-αI偶联神经调节剂(去甲肾上腺素和γ-氨基丁酸)是否作为谷氨酸能突触传递的冗余调节因子。我们的结果表明，在第5层锥体神经元的单个树突棘中，α-2肾上腺素能受体(α-2Rs)选择性地抑制AMPA型谷氨酸受体介导的兴奋性传递，而B型GABA受体(GABABRs)则抑制NMDA型受体。我们发现这两种调节剂都通过下调cAMP和PKA发挥作用。然而，通过限制活性GαI的寿命，RGS4促进了对这两个不同的靶蛋白的独立控制。我们的发现强调了一种机制，通过这种机制，神经调节微域可以在亚细胞间隔中建立，如树突棘。
A diverse array of neuromodulators governs cellular function in the prefrontal cortex (PFC) via the activation of G protein-coupled receptors (GPCRs). However, these functionally diverse signals are carried and amplified by a relatively small assortment of intracellular second messengers. Here, we examined whether two distinct Gαi-coupled neuromodulators (norepinephrine and GABA) act as redundant regulators of glutamatergic synaptic transmission. Our results reveal that, within single dendritic spines of layer 5 pyramidal neurons, alpha-2 adrenergic receptors (α2Rs) selectively inhibit excitatory transmission mediated by AMPA-type glutamate receptors while Type B GABA receptors (GABABRs) inhibit NMDA-type receptors. We show that both modulators act via the downregulation of cAMP and PKA. However, by restricting the lifetime of active Gαi, RGS4 promotes the independent control of these two distinct target proteins. Our findings highlight a mechanism by which neuromodulatory microdomains can be established in subcellular compartments such as dendritic spines.