Sonic hedgehog regulates presynaptic terminal size, ultrastructure and function in hippocampal neurons
Sonic hedgehog regulates presynaptic terminal size, ultrastructure and function in hippocampal neurons
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DOI：
10.1242/jcs.105080
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发表时间：
2012-09-15
影响因子：
4
通讯作者：
Yao, Pamela J.
中科院分区：
文献类型：
--
作者：
Mitchell, Nicholas;Petralia, Ronald S.;Yao, Pamela J.
Sonic hedgehog(Shh)信号对胚胎神经管的形成是必不可少的，但它在大脑中有丝分裂后分化的神经元中的存在和功能在很大程度上仍不清楚。我们最近发现Shh及其信号成分Patch和Smoothed在出生后和成年海马神经元中表达。我们现在已经研究了Shh信号是否在这些神经元中起作用。以培养的海马神经元为模型系统，我们发现突触前终末对Shh的应用有明显的反应。超微结构检查证实了突触前轮廓的扩大，并显示突触小泡的大小不同程度地增加，导致一致性的丧失。此外，电生理分析显示，Shh引起的自发微小兴奋性突触后电流(MEPSCs)的频率显著增加，但幅度没有显著增加，这为Shh在突触前终末的选择性作用提供了功能证据。因此，我们得出结论，Shh信号调节海马神经元突触前终末的结构和功能特性。
Sonic hedgehog (Shh) signaling is essential to the patterning of the embryonic neural tube, but its presence and function in the postmitotic differentiated neurons in the brain remain largely uncharacterized. We recently showed that Shh and its signaling components, Patched and Smoothened, are expressed in postnatal and adult hippocampal neurons. We have now examined whether Shh signaling has a function in these neurons. Using cultured hippocampal neurons as a model system, we found that presynaptic terminals become significantly larger in response to the application of Shh. Ultrastructural examination confirmed the enlarged presynaptic profiles and also revealed variable increases in the size of synaptic vesicles, with a resulting loss of uniformity. Furthermore, electrophysiological analyses showed significant increases in the frequency, but not the amplitude, of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in response to Shh, providing functional evidence of the selective role of Shh in presynaptic terminals. Thus, we conclude that Shh signaling regulates the structure and functional properties of presynaptic terminals of hippocampal neurons.