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首页> 外文期刊>The European Journal of Neuroscience >Effects of the GABA(A) receptor antagonists bicuculline and gabazine on stimulus-induced sharp wave-ripple complexes in adult rat hippocampus in vitro.
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Effects of the GABA(A) receptor antagonists bicuculline and gabazine on stimulus-induced sharp wave-ripple complexes in adult rat hippocampus in vitro.

机译：GABA（A）受体拮抗剂比库林和加巴嗪对成年大鼠海马体外刺激引起的尖波波纹复合体的影响。

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摘要

Hippocampal sharp wave-ripple-complexes (SPW-Rs) are characterized by slow field potential transients superimposed by ripples with a frequency of approximately 200 Hz. In epileptic humans and rats frequencies of such transient network oscillations can reach up to 500 Hz potentially due to loss of functional inhibition. Therefore, we investigated whether GABA(A) receptor antagonists increased ripple frequency during SPW-Rs. Within area CA3, SPW-Rs were induced by repeated stimulation of stratum radiatum in area CA1 of adult Wistar rat hippocampal slices. Intracellular recordings showed that in approximately 50% of recorded CA3 pyramidal cells SPW-Rs were accompanied by compound excitory postsynaptic potentials (EPSPs) of approximately 10 mV superimposed by up to four action potentials (APs). The remaining cells responded with a compound inhibitory postsynaptic potential (IPSP) during SPW-Rs. The GABA(A) receptor antagonists bicuculline (BMI) or gabazine (SR-95531) led to a transition of SPW-Rs into prolonged bursts with a significant increase in amplitude and duration reminiscent of recurrent epileptiform discharges (REDs). Ripple frequencies increased from approximately 190 Hz to approximately 300 Hz. In naive slices SR-95531 and BMI also evoked REDs with similar incidence and high frequency ripple frequencies of approximately 240 Hz. Elevations in extracellular potassium concentration during REDs were approximately 20-fold higher than those observed during SPW-Rs. Intracellular recordings revealed bursts that were characterized by a large (> 25 mV) prolonged depolarization superimposed by up to 40 APs in close synchrony with extracellularly recorded ripples. Our results suggest that the generation of high frequency ripples, which are also observed in epileptic humans and rats, could indicate a loss of functional inhibition.
机译：海马尖波波纹复合体（SPW-Rs）的特征是场势瞬变缓慢，并由频率约为200 Hz的脉动叠加。在癫痫的人类和大鼠中，这种瞬态网络振荡的频率可能会由于功能抑制的丧失而达到500 Hz。因此，我们调查了GABA（A）受体拮抗剂是否在SPW-Rs期间增加了波纹频率。在CA3区域内，通过重复刺激成年Wistar大鼠海马切片CA1区域的放射状层来诱导SPW-Rs。细胞内记录显示，在大约50％的CA3锥体细胞中，SPW-R伴随着大约10 mV的复合兴奋性突触后电位（EPSP），最多可叠加四个动作电位（AP）。其余细胞在SPW-R期间以复合抑制突触后电位（IPSP）应答。 GABA（A）受体拮抗剂双小分子（BMI）或gabazine（SR-95531）导致SPW-R过渡为长时间爆发，其幅度和持续时间显着增加，令人联想到复发性癫痫样放电（RED）。纹波频率从大约190 Hz增加到大约300 Hz。在天真切片中，SR-95531和BMI还诱发了具有相似入射和大约240 Hz的高频纹波频率的RED。 RED期间细胞外钾浓度的升高比SPW-R期间观察到的升高约20倍。细胞内的记录揭示了爆发，其特征是大的（> 25 mV）延长的去极化与多达40个AP叠加，与细胞外记录的涟漪紧密同步。我们的结果表明，在癫痫的人和大鼠中也观察到了高频纹波的产生，这可能表明功能抑制的丧失。

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