You Snooze You Seize: GABAergic Potentiation of Genetic Generalized Seizures During NREM.
You Snooze You Seize: GABAergic Potentiation of Genetic Generalized Seizures During NREM.
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DOI：
10.1177/15357597211012454
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发表时间：
2021-07
影响因子：
3.6
通讯作者：
Kadam SD
中科院分区：
文献类型：
--
作者：
Kadam SD
GABA 能突触电流的状态依赖性增强受损会引发遗传性全面性癫痫模型中的癫痫发作 张 C-Q、Catron MA、Ding L、Hanna CM、Gallagher MJ、Macdonald RL、Zhou C. Cereb Cortex。 2021；31(2)：768-784。 doi：10.1093/cercor/bhaa256。 https://pubmed.ncbi.nlm.nih.gov/32930324/ 遗传性全面性癫痫（GGE）患者的癫痫活动优先出现在睡眠期间，其机制仍不清楚。在这里，我们发现类似睡眠的慢波振荡（0.5 Hz SWO）增强了野生型（wt）小鼠脑切片的第五层皮质锥体神经元的兴奋性和抑制性突触电流。相比之下，SWO 增强了 Dravet 癫痫综合征杂合 (het) 敲入 (KI) Gabrg2+Q/390X 模型中皮质神经元的兴奋性电流，但不增强抑制性电流。这造成了诱发的兴奋性电流和抑制性电流之间的不平衡，从而有效地促进神经元动作电位的放电。同样，皮层神经元中生理上相似的上/下状态诱导（存在于慢波睡眠期间）也增强了 wt 和 het KI 小鼠脑切片内的兴奋性突触电流。此外，兴奋性突触电流的这种状态依赖性增强需要一些稳态突触可塑性的信号通路。因此，在 het KI 小鼠中，体内 SWO 诱导（使用光遗传学方法）引发全身性癫痫尖峰波放电 (SWD)，并伴有突然不动、面部肌阵挛和触须抽搐。相比之下，在野生型同窝小鼠中，SWO 诱导不会引起癫痫性 SWD 和运动行为。据我们所知，这是第一个解释为什么癫痫性 SWD 优先发生在人类 GGE 患者的非快速动眼睡眠和安静觉醒期间的机制。
Impaired State-Dependent Potentiation of GABAergic Synaptic Currents Triggers Seizures in a Genetic Generalized Epilepsy Model Zhang C-Q, Catron MA, Ding L, Hanna CM, Gallagher MJ, Macdonald RL, Zhou C. Cereb Cortex. 2021;31(2):768-784. doi:10.1093/cercor/bhaa256. https://pubmed.ncbi.nlm.nih.gov/32930324/ Epileptic activity in genetic generalized epilepsy (GGE) patients preferentially appears during sleep and its mechanism remains unknown. Here, we found that sleep-like slow-wave oscillations (0.5 Hz SWOs) potentiated excitatory and inhibitory synaptic currents in layer V cortical pyramidal neurons from wild-type (wt) mouse brain slices. In contrast, SWOs potentiated excitatory, but not inhibitory, currents in cortical neurons from a heterozygous (het) knock-in (KI) Gabrg2+Q/390X model of Dravet epilepsy syndrome. This created an imbalance between evoked excitatory and inhibitory currents to effectively prompt neuronal action potential firings. Similarly, physiologically similar up-/down-state induction (present during slow-wave sleep) in cortical neurons also potentiated excitatory synaptic currents within brain slices from wt and het KI mice. Moreover, this state-dependent potentiation of excitatory synaptic currents entailed some signaling pathways of homeostatic synaptic plasticity. Consequently, in het KI mice, in vivo SWO induction (using optogenetic methods) triggered generalized epileptic spike-wave discharges (SWDs), being accompanied by sudden immobility, facial myoclonus, and vibrissa twitching. In contrast, in wt littermates, SWO induction did not cause epileptic SWDs and motor behaviors. To our knowledge, this is the first mechanism to explain why epileptic SWDs preferentially happen during non-rapid eye-movement sleep and quiet-wakefulness in human GGE patients.
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影响因子：
2.4
作者：
Foldvary-Schaefer, N;Grigg-Damberger, M
通讯作者：
Grigg-Damberger, M
影响因子：
5.6
作者：
Huang X;Zhou C;Tian M;Kang JQ;Shen W;Verdier K;Pimenta A;MacDonald RL
通讯作者：
MacDonald RL
影响因子：
3.7
作者：
Ammanuel S;Chan WC;Adler DA;Lakshamanan BM;Gupta SS;Ewen JB;Johnston MV;Marcus CL;Naidu S;Kadam SD
通讯作者：
Kadam SD
影响因子：
--
作者：
Riedner, Brady A.;Hulse, Bradley K.;Murphy, Michael J.;Ferrarelli, Fabio;Tononi, Giulio
通讯作者：
Tononi, Giulio
影响因子：
4.7
作者：
Lo Barco, Tommaso;Kaminska, Anna;Nabbout, Rima
通讯作者：
Nabbout, Rima