Astrocytic iNOS-Dependent Enhancement of Synaptic Release in Mouse Neocortex

Astrocytic iNOS-Dependent Enhancement of Synaptic Release in Mouse Neocortex
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DOI:
10.1152/jn.00676.2009
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发表时间:
2010-03-01
影响因子:
2.5
通讯作者:
Amitai, Yael
Amitai, Yael
中科院分区:
医学3区
文献类型:
--
作者:
Buskila, Yossi;Amitai, Yael

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Buskila Y,Amitai Y。星形细胞 iNOS 依赖性增强小鼠新皮质突触释放。 J Neurophysiol 103: 1322-1328, 2010。首次发表于 2010 年 1 月 13 日; doi:10.1152/jn.00676.2009。一氧化氮(NO)已被认为是影响突触传递的非典型神经元信使,但其细胞来源仍未解决,因为新皮质等大脑区域中的神经元一氧化氮合酶亚型(nNOS)仅由一小部分抑制性神经元表达。神经胶质一氧化氮合酶异构体 (iNOS) 在调节神经元活动中的作用在很大程度上被忽视,因为人们普遍认为这种酶是受到有害刺激后基因诱导的调节。使用小鼠新皮质的急性脑切片和电生理学,我们发现选择性抑制 iNOS 会减少自发和诱发的突触释放。此外,iNOS 抑制部分阻止和逆转了 2/3 层锥体神经元兴奋性突触的增强。 NOS 酶测定证实了一个小但可靠的 Ca2+ 独立活性部分,与组织中功能性 iNOS 的存在一致。这些数据共同表明星形胶质细胞是新皮质突触释放亚硝化调节的来源。
Buskila Y, Amitai Y. Astrocytic iNOS-dependent enhancement of synaptic release in mouse neocortex. J Neurophysiol 103: 1322-1328, 2010. First published January 13, 2010; doi: 10.1152/jn.00676.2009. Nitric oxide (NO) has been recognized as an atypical neuronal messenger affecting synaptic transmission, but its cellular source has remained unresolved as the neuronal NO synthase isoform ( nNOS) in brain areas such as the neocortex is expressed only by a small subset of inhibitory neurons. The involvement of the glial NOS isoform ( iNOS) in modulating neuronal activity has been largely ignored because it has been accepted that this enzyme is regulated by gene induction following detrimental stimuli. Using acute brain slices from mouse neocortex and electrophysiology, we found that selective inhibition of iNOS reduced both spontaneous and evoked synaptic release. Moreover, iNOS inhibition partially prevented and reversed the potentiation of excitatory synapses in layer 2/3 pyramidal neurons. NOS enzymatic assay confirmed a small but reliable Ca2+-independent activity fraction, consistent with the existence of functioning iNOS in the tissue. Together these data point to astrocytes as a source for the nitrosative regulation of synaptic release in the neocortex.