Neuregulin1 downregulates postsynaptic GABAA receptors at the hippocampal inhibitory synapse
Neuregulin1 downregulates postsynaptic GABAA receptors at the hippocampal inhibitory synapse
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DOI：
10.1002/hipo.10185
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发表时间：
2004-01-01
期刊：
影响因子：
3.5
通讯作者：
Corfas, G
中科院分区：
文献类型：
--
作者：
Okada, M;Corfas, G
生长因子神经调节蛋白1 （NRG1）通过上调特定神经递质受体亚单位的表达，参与神经肌肉突触和神经元间突触的形成和成熟。在本报告中，我们发现，在海马中，NRG1的表达模式表明它调节CA1区域的突触发育。然而，与其他突触的研究结果相反，NRG1降低了海马切片中γ -氨基丁酸（GABA）A受体亚基的表达，以及海马CA1锥体神经元中GABA能微型抑制性突触后电流（IPSCs）的平均振幅，而不影响IPSC动力学或频率。NRG1的这些作用发生时，谷氨酸受体和其他突触蛋白并没有随之改变。我们提出NRG1在海马抑制性突触形成和成熟中的作用是下调而不是上调受体亚基表达。这些结果表明，NRG1可能导致出生后早期发育过程中海马CA1锥体神经元gaba能突触活性的降低，并且海马NRG1信号的改变可能导致精神分裂症和癫痫。(C) 2004 Wiley-Liss, Inc。
The growth factor neuregulin 1 (NRG1) has been proposed to contribute to the formation and maturation of neuromuscular and interneuronal synapses by upregulating the expression of specific neurotransmitter receptor subunits. In the present report, we show that, in the hippocampus, NRG1 is expressed in a pattern suggesting that it regulates synapse development in the CA1 region. However, in contrast to what has been shown in other synapses, NRG1 reduces the expression of gamma-aminobutyric acid (GABA)A receptors a subunits in hippocampal slices, and the mean amplitude of GABAergic miniature inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal neurons, without affecting IPSC kinetics or frequency. These effects of NRG1 occur without concomitant changes in glutamate receptors and other synaptic proteins. We propose that the role of NRG1 in the formation and maturation in the hippocampal inhibitory synapse is downregulation, rather than upregulation, of receptor subunit expression. These results suggest that NRG1 may contribute to the reduction in GABAergic synaptic activity in hippocampal CA1 pyramidal neurons that normally occurs during early postnatal development, and that alterations in NRG1 signaling in the hippocampus may contribute to schizophrenia and epilepsy. (C) 2004 Wiley-Liss, Inc.