Altered hippocampal interneuron activity precedes ictal onset
Altered hippocampal interneuron activity precedes ictal onset
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DOI：
10.7554/elife.40750
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发表时间：
2018-11-02
期刊：
影响因子：
7.7
通讯作者：
Cardin, Jessica A.
中科院分区：
文献类型：
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作者：
Miri, Mitra L.;Vinck, Martin;Cardin, Jessica A.
虽然gaba能抑制失败是癫痫发作的一种普遍假设机制，但导致从健康活动迅速转变为癫痫活动的一系列事件仍不清楚。此外，抑制性中间神经元种群的多样性对理解癫痫发作时局部电路的相互作用提出了挑战。采用光遗传学和电生理学相结合的方法，我们在体内检测了化学惊厥诱导小鼠海马中间神经元类的活性。令人惊讶的是，来自小白蛋白（PV）和生长抑素表达（SST）中间神经元的突触抑制在整个痫前期和痫前期保持完整。然而，这两种抑制源在其前部放电模式和对输入的敏感性上表现出细胞类型特异性差异。我们的研究结果表明，突发活动的开始与这些中间神经元的放电丧失或突触抑制的失败无关，而是与这些中间神经元在海马体回路中各自角色的中断有关。
Although failure of GABAergic inhibition is a commonly hypothesized mechanism underlying seizure disorders, the series of events that precipitate a rapid shift from healthy to ictal activity remain unclear. Furthermore, the diversity of inhibitory interneuron populations poses a challenge for understanding local circuit interactions during seizure initiation. Using a combined optogenetic and electrophysiological approach, we examined the activity of identified mouse hippocampal interneuron classes during chemoconvulsant seizure induction in vivo. Surprisingly, synaptic inhibition from parvalbumin- (PV) and somatostatin-expressing (SST) interneurons remained intact throughout the preictal period and early ictal phase. However, these two sources of inhibition exhibited cell-type-specific differences in their preictal firing patterns and sensitivity to input. Our findings suggest that the onset of ictal activity is not associated with loss of firing by these interneurons or a failure of synaptic inhibition but is instead linked with disruptions of the respective roles these interneurons play in the hippocampal circuit.