The self-regulating nature of spontaneous synchronized activity in developing mouse cortical neurones

The self-regulating nature of spontaneous synchronized activity in developing mouse cortical neurones
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DOI:
10.1113/jphysiol.2006.117523
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发表时间:
2006-11-15
影响因子:
5.5
通讯作者:
Moody, William J.
Moody, William J.
中科院分区:
医学1区
文献类型:
--
作者:
McCabe, Annette K.;Chisholm, Sarah L.;Moody, William J.

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大量神经元之间高度同步的自发电活动波出现在整个发育中的哺乳动物中枢神经系统中。这一活动发生的阶段受到严格管制,以便能够正确地启动依赖活动的发展方案。然而,是什么决定了神经系统特定区域自发同步活动(SSA)的开始和停止,目前仍不清楚。我们已经验证了这样的假设,即活动本身触发内在和电路特性的发育变化,这些特性决定了SSA发生的阶段。为此,我们将培养的小鼠新皮质切片暴露于河豚毒素(TTX)以阻断SSA,SSA通常发生在胚胎第17天(E17)到出生后第3天(P3)。在对照培养的切片中,SSA在P3后很少发生。然而,在TTX处理的切片中,SSA至少从P3(去除TTX的那一天)到P10产生。这表明,在没有自发活动的情况下,正常情况下决定SSA发生时间的机制没有启动,并且发生了将SSA发生的时间转移到发育后期的代偿反应。
Waves of spontaneous electrical activity that are highly synchronized across large populations of neurones occur throughout the developing mammalian central nervous system. The stages at which this activity occurs are tightly regulated to allow activity-dependent developmental programmes to be initiated correctly. What determines the onset and cessation of spontaneous synchronous activity (SSA) in a particular region of the nervous system, however, remains unclear. We have tested the hypothesis that activity itself triggers developmental changes in intrinsic and circuit properties that determine the stages at which SSA occurs. To do this we exposed cultured slices of mouse neocortex to tetrodotoxin (TTX) to block SSA, which normally occurs between embryonic day 17 (E17) and postnatal day 3 (P3). In control cultured slices, SSA rarely occurs after P3. In TTX-treated slices, however, SSA was generated from P3 (the day of TTX removal) until at least P10. This indicates that in the absence of spontaneous activity, the mechanisms that normally determine the timing of SSA are not initiated, and that a compensatory response occurs that shifts the time of SSA occurrence to later developmental stages.