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Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures
BMC Neuroscience ( IF 2.4 ) Pub Date : 2019-12-01 , DOI: 10.1186/s12868-019-0540-6
Matthias Kreuzer 1 , Paul S García 2 , Verena Brucklacher-Waldert 3, 4 , Rebecca Claassen 3, 5 , Gerhard Schneider 1 , Bernd Antkowiak 3, 6 , Berthold Drexler 3
Affiliation  

BackgroundThe pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic and sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons.MethodWe used electrophysiological recordings from organotypic slice cultures derived from Sprague–Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM, n = 7) or ethanol (30 and 60 mM, n = 11) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase.ResultsWhile both substances seem to decrease neocortical action potential firing in a not significantly different (p = 0.659, Mann–Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p < 0.05). Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam for a wide frequency range and a narrow-band de-synchronizing effect for ethanol (p < 0.05, Kolmogorov–Smirnov test).ConclusionDiazepam and ethanol, induce specific patterns of network depressant actions. Diazepam induces cortical network inhibition and increased synchronicity via gamma subunit containing GABAA receptors. Ethanol also induces cortical network inhibition, but without an increase in synchronicity via a wider span of molecular targets.

中文翻译:

地西泮和乙醇不同地调节器官皮层培养物中的神经元活动

背景地西泮和乙醇给药的药效学结果相似,均能介导遗忘和镇静催眠作用。尽管这些分子中的每一个都有效地降低了中枢神经元的活性,但地西泮是通过调节一组更具体的受体靶标(含有 γ 亚基的 GABAA 受体)来实现的,而酒精对其受体生物活性的选择性较低。我们的研究侧重于地西泮和乙醇对培养的皮层神经元放电模式的不同作用。方法我们使用来自 Sprague-Dawley 大鼠新皮层的器官切片培养物的电生理记录。我们将这些培养物暴露于地西泮(15 和 30 µM,n = 7)或乙醇(30 和 60 mM,n = 11)并记录基线和实验条件下的电活动。为了分析,我们提取了自发活动的情节,即皮层向上状态。在分离动作电位和局部场电位 (LFP) 活动后,我们观察了动作电位数量、LFP 光谱功率以及动作电位和 LFP 相之间耦合的差异。为了以没有显着差异(p = 0.659,Mann-Whitney U)的方式减少新皮质动作电位放电,地西泮增加了上态的光谱功率而不显着影响光谱组成,而乙醇不会显着改变光谱功率但弗里德曼检验和 Bonferroni 校正揭示的上升状态的振荡结构(p < 0.05)。更多,LFP 相位耦合的动作电位揭示了地西泮对宽频率范围的同步作用和对乙醇的窄带去同步作用(p < 0.05,Kolmogorov-Smirnov 检验)。结论地西泮和乙醇,诱导特定的网络模式抑郁动作。地西泮通过含有 GABAA 受体的 γ 亚基诱导皮质网络抑制和增加同步性。乙醇还诱导皮质网络抑制,但不会通过更广泛的分子靶标增加同步性。地西泮通过含有 GABAA 受体的 γ 亚基诱导皮质网络抑制和增加同步性。乙醇还诱导皮质网络抑制,但不会通过更广泛的分子靶标增加同步性。地西泮通过含有 GABAA 受体的 γ 亚基诱导皮质网络抑制和增加同步性。乙醇还诱导皮质网络抑制,但不会通过更广泛的分子靶标增加同步性。
更新日期:2019-12-01
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