Effects of the GABA‐uptake blocker NNC‐711 on spontaneous sharp wave–ripple complexes in mouse hippocampal slices

Effects of the GABA‐uptake blocker NNC‐711 on spontaneous sharp wave–ripple complexes in mouse hippocampal slices
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GABAα摄取阻滞剂NNCα711对小鼠海马切片自发锐波波纹复合物的影响

DOI:
10.1002/hipo.22104
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发表时间:
2013
期刊:
影响因子:
3.5
通讯作者:
Both M
Both M
中科院分区:
医学3区
文献类型:
--
作者:
Viereckel T;Kostic M;Bähner F;Draguhn A;Both M

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皮层网络中神经元精确的时间和空间活动模式由不同的状态依赖型网络振荡组织。GABA能抑制在这种振荡的潜在机制中起着关键作用,并且已经表明广泛分布的相位抑制性突触后电位(IPSP)的持续时间决定了所产生的网络振荡的频率。在这里,我们在尖波波纹(SPW-R)复合物的体外模型中测试了这一假设,这是一种在200 Hz的网络振荡的特别快的模式,涉及记忆巩固。我们在不存在和存在NCC-711(GABA摄取抑制剂)的情况下记录了小鼠海马切片中的SPW-R。IPSP的延长导致SPW-R的发生减少,而叠加的快速振荡以及节律细胞同步的精度保持稳定。应用地西泮(GABA A受体的正调节剂)得到一致的结果。我们得出结论,相位抑制是CA 3(SPW-R产生的地方)网络兴奋性的主要调节器,但不会设置海马波纹的频率。© 2013威利期刊公司.
The precise temporal and spatial activity patterns of neurons in cortical networks are organized by different state‐dependent types of network oscillations. GABAergic inhibition plays a key role in the underlying mechanisms of such oscillations and it has been suggested that the duration of widely distributed phasic inhibitory postsynaptic potentials (IPSPs) determines the frequency of the resulting network oscillation. Here, we test this hypothesis in an in vitro model of sharp wave–ripple (SPW‐R) complexes, a particularly fast pattern of network oscillations at ∼200 Hz which is involved in memory consolidation. We recorded SPW‐R in mouse hippocampal slices in the absence and presence of NCC‐711, an inhibitor of GABA uptake. The resulting prolongation of IPSP resulted in reduced occurrence of SPW‐R, whereas the superimposed fast oscillations as well as the precision of rhythmic cell synchronization remained stable. Application of Diazepam which is a positive modulator of the GABAAreceptor led to consistent results. We conclude that phasic inhibition is a major regulator of network excitability in CA3 (where SPW‐Rs are generated), but does not set the frequency of hippocampal ripples. © 2013 Wiley Periodicals, Inc.
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