Volume-transmitted GABA waves pace epileptiform rhythms in the hippocampal network.
Volume-transmitted GABA waves pace epileptiform rhythms in the hippocampal network.
复制标题
DOI：
10.1016/j.cub.2023.02.051
复制
发表时间：
2023-04-10
期刊：
影响因子：
9.2
通讯作者：
Rusakov, Dmitri A.
中科院分区：
文献类型：
--
作者：
Magloire, Vincent;Savtchenko, Leonid P.;Jensen, Thomas P.;Sylantyev, Sergyi;Tyurikova, Olga;Cole, Nicholas;Tyurikova, Olga;Kullmann, Dimitri M.;Walker, Matthew C.;Marvin, Jonathan S.;Looger, Loren L.;Hasseman, Jeremy P.;Kolb, Ilya;Pavlov, Ivan;Rusakov, Dmitri A.
关于癫痫样节律性放电的机制仍有争议。传统上，对它们的理解集中在由突触GABA能连接驱动的神经元间网络上。然而，同步的神经元间放电也可以触发跨组织体积的细胞外GABA的瞬时升高，从而提高突触和突触外GABA受体在多个细胞中的紧张性电导（Gtonic）。在这里，我们使用膜片钳GABA“嗅探器”和一种新的光学GABA传感器监测海马切片中的细胞外GABA，表明周期性癫痫样放电之前的短暂的，区域范围内的细胞外GABA波。神经网络模拟，将体积传输的GABA信号指向GABA驱动的网络抑制和去抑制的循环，支持这种关系。我们使用多个神经元的同时膜片钳记录和快速尖峰中间神经元的选择性光遗传学刺激来测试和验证这一假设。重要的是，减少GABA摄取以减缓细胞外GABA波动-而不影响突触GABA能传递或静息GABA水平-减缓节律活动。因此，我们的研究结果揭示了突触外，体积传输的GABA在起搏大脑网络的再生节律活动的关键作用。GABA嗅探器和光学传感器报告[GABA]e在发作间期事件之前升高神经元间网络模型将节律性与体积传输的GABA作用相关多细胞记录支持周期性GABA驱动的去抑制GABA转运蛋白调节发作间期事件的节律的概念Magloire et al.表明周期性癫痫样放电之前是细胞外GABA的瞬态波，这对这种脑网络节律的定时至关重要。
Mechanisms that entrain and pace rhythmic epileptiform discharges remain debated. Traditionally, the quest to understand them has focused on interneuronal networks driven by synaptic GABAergic connections. However, synchronized interneuronal discharges could also trigger the transient elevations of extracellular GABA across the tissue volume, thus raising tonic conductance (Gtonic) of synaptic and extrasynaptic GABA receptors in multiple cells. Here, we monitor extracellular GABA in hippocampal slices using patch-clamp GABA “sniffer” and a novel optical GABA sensor, showing that periodic epileptiform discharges are preceded by transient, region-wide waves of extracellular GABA. Neural network simulations that incorporate volume-transmitted GABA signals point to a cycle of GABA-driven network inhibition and disinhibition underpinning this relationship. We test and validate this hypothesis using simultaneous patch-clamp recordings from multiple neurons and selective optogenetic stimulation of fast-spiking interneurons. Critically, reducing GABA uptake in order to decelerate extracellular GABA fluctuations—without affecting synaptic GABAergic transmission or resting GABA levels—slows down rhythmic activity. Our findings thus unveil a key role of extrasynaptic, volume-transmitted GABA in pacing regenerative rhythmic activity in brain networks. GABA sniffer and optical sensor report [GABA]e rises before interictal events Interneuronal network models relate rhythmicity to volume-transmitted GABA actions Multi-cell recordings support the concept of periodical GABA-driven disinhibition GABA transporters tune the rhythms of interictal events Magloire et al. show that periodic epileptiform discharges are preceded by transient waves of extracellular GABA, which appear critical for the timing of such brain network rhythms.
登录
查看更多内容
影响因子：
64.8
作者：
COBB, SR;BUHL, EH;SOMOGYI, P
通讯作者：
SOMOGYI, P
影响因子：
3.4
作者：
Bicho, A;Grewer, C
通讯作者：
Grewer, C
谷氨酸摄取触发转运蛋白介导的GABA从星形胶质细胞释放。
影响因子：
3.7
作者：
Héja L;Barabás P;Nyitrai G;Kékesi KA;Lasztóczi B;Toke O;Tárkányi G;Madsen K;Schousboe A;Dobolyi A;Palkovits M;Kardos J
通讯作者：
Kardos J
影响因子：
11.2
作者：
Gnatkovsky, Vadym;Librizzi, Laura;de Curris, Marco
通讯作者：
de Curris, Marco
影响因子：
2.5
作者：
HUGUENARD, JR;MCCORMICK, DA
通讯作者：
MCCORMICK, DA