Neuregulin-1 enhances depolarization-induced GABA release
Neuregulin-1 enhances depolarization-induced GABA release
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DOI：
10.1016/j.neuron.2007.04.009
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发表时间：
2007-05-24
期刊：
影响因子：
16.2
通讯作者：
Mei, Lin
中科院分区：
文献类型：
--
作者：
Woo, Ran-Sook;Li, Xiao-Ming;Mei, Lin
神经发育调节素-1(NRG1)是一种神经发育调节剂，已被证明调节兴奋性突触的神经传递。尽管ErbB4是一种关键的NRG1受体，在谷氨酸脱羧酶(GAD)阳性神经元中表达，但对其在GABA能传递中的作用知之甚少。我们发现ErbB4定位于前额叶皮质的GABA能终末。我们的数据表明，内源性和外源性NRG1在调节GABA能传递方面发挥了作用。这种作用被ErbB4的抑制或突变所阻断，这表明ErbB4参与了这一过程。综上所述，这些结果表明，NRG1通过突触前ErbB4受体调节GABA能传递，鉴定了NRG1的一种新功能。由于NRG1和ErbB4都是精神分裂症的易感基因，这些观察结果可能提示了这种疾病中GABA能神经传递异常的机制。
Neuregulin-1 (NRG1), a regulator of neural development, has been shown to regulate neurotransmission at excitatory synapses. Although ErbB4, a key NRG1 receptor, is expressed in glutamic acid decarboxylase (GAD)-positive neurons, little is known about its role in GABAergic transmission. We show that ErbB4 is localized at GABAergic terminals of the prefrontal cortex. Our data indicate a role of NRG1, both endogenous and exogenous, in regulation of GABAergic transmission. This effect was blocked by inhibition or mutation of ErbB4, suggesting the involvement of ErbB4. Together, these results indicate that NRG1 regulates GABAergic transmission via presynaptic ErbB4 receptors, identifying a novel function of NRG1. Because both NRG1 and ErbB4 have emerged as susceptibility genes of schizophrenia, these observations may suggest a mechanism for abnormal GABAergic neurotransmission in this disorder.