Khalilov Ilgam, Minlebaev Marat, Mukhtarov Marat, Juzekaeva Elvira, Khazipov Roustem
INMED-INSERM, Aix-Marseille UniversityMarseille, France.
Laboratory of Neurobiology, Kazan Federal UniversityKazan, Russia.
Front Cell Neurosci. 2017 Jun 28;11:179. doi: 10.3389/fncel.2017.00179. eCollection 2017.
During development, hippocampal CA3 network generates recurrent population bursts, so-called Giant Depolarizing Potentials (GDPs). GDPs are characterized by synchronous depolarization and firing of CA3 pyramidal cells followed by afterhyperpolarization (GDP-AHP). Here, we explored the properties of GDP-AHP in CA3 pyramidal cells using gramicidin perforated patch clamp recordings from neonatal rat hippocampal slices. We found that GDP-AHP occurs independently of whether CA3 pyramidal cells fire action potentials (APs) or remain silent during GDPs. However, the amplitude of GDP-AHP increased with the number of APs the cells fired during GDPs. The reversal potential of the GDP-AHP was close to the potassium equilibrium potential. During voltage-clamp recordings, current-voltage relationships of the postsynaptic currents activated during GDP-AHP were characterized by reversal near the potassium equilibrium potential and inward rectification, similar to the responses evoked by the GABA(B) receptor agonists. Finally, the GABA(B) receptor antagonist CGP55845 strongly reduced GDP-AHP and prolonged GDPs, eventually transforming them to the interictal and ictal-like discharges. Together, our findings suggest that the GDP-AHP involves two mechanisms: (i) postsynaptic GABA(B) receptor activated potassium currents, which are activated independently on whether the cell fires or not during GDPs; and (ii) activity-dependent, likely calcium activated potassium currents, whose contribution to the GDP-AHP is dependent on the amount of firing during GDPs. We propose that these two complementary inhibitory postsynaptic mechanisms cooperate in the termination of GDP.
在发育过程中,海马体CA3网络会产生反复出现的群体爆发,即所谓的巨大去极化电位(GDPs)。GDPs的特征是CA3锥体细胞同步去极化和放电,随后是超极化后电位(GDP-AHP)。在这里,我们使用新生大鼠海马切片的短杆菌肽穿孔膜片钳记录来探索CA3锥体细胞中GDP-AHP的特性。我们发现,GDP-AHP的出现与CA3锥体细胞在GDP期间是否发放动作电位(APs)或保持沉默无关。然而,GDP-AHP的幅度随着细胞在GDP期间发放的AP数量增加而增大。GDP-AHP的反转电位接近钾平衡电位。在电压钳记录期间,GDP-AHP期间激活的突触后电流的电流-电压关系的特征是在钾平衡电位附近反转和内向整流,类似于GABA(B)受体激动剂诱发的反应。最后,GABA(B)受体拮抗剂CGP55845强烈降低了GDP-AHP并延长了GDPs,最终将它们转变为发作间期和发作样放电。总之,我们的研究结果表明,GDP-AHP涉及两种机制:(i)突触后GABA(B)受体激活的钾电流,其在GDP期间细胞是否放电的情况下独立激活;(ii)活动依赖性的、可能是钙激活的钾电流,其对GDP-AHP的贡献取决于GDP期间的放电量。我们提出,这两种互补的抑制性突触后机制在GDP的终止中协同作用。