Activity-dependent regulation of inhibitory synapse development by Npas4.

Activity-dependent regulation of inhibitory synapse development by Npas4.
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DOI:
10.1038/nature07319
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发表时间:
2008-10-30
期刊:
影响因子:
64.8
通讯作者:
Greenberg, Michael E.
Greenberg, Michael E.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lin, Yingxi;Bloodgood, Brenda L.;Hauser, Jessica L.;Lapan, Ariya D.;Koon, Alex C.;Kim, Tae-Kyung;Hu, Linda S.;Malik, Athar N.;Greenberg, Michael E.

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神经元活动调节哺乳动物大脑中兴奋性和抑制性突触的发育和成熟。最近的几项研究已经确定了神经元中控制兴奋性突触发育的信号网络。然而,关于调节GABA(γ-氨基丁酸)释放抑制性突触活性依赖性发育的分子机制却知之甚少。在这里,我们报道了一种转录因子Npas4,它通过调节活性依赖基因的表达在抑制性突触的发展中发挥作用,进而控制兴奋性神经元上形成的GABA释放突触的数量。这些发现表明,活性依赖的基因程序调节抑制性突触的发育,并表明该程序在控制突触兴奋和抑制之间的动态平衡方面发挥了新的作用。
Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity-dependent development of GABA (γ-aminobutyric acid)-releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons. These findings demonstrate that the activity-dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.
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