Chronic loss of inhibition in piriform cortex following brief, daily optogenetic stimulation.
Chronic loss of inhibition in piriform cortex following brief, daily optogenetic stimulation.
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DOI：
10.1016/j.celrep.2021.109001
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发表时间：
2021-04-20
期刊：
影响因子：
8.8
通讯作者：
Franks KM
中科院分区：
文献类型：
--
作者：
Ryu B;Nagappan S;Santos-Valencia F;Lee P;Rodriguez E;Lackie M;Takatoh J;Franks KM
癫痫发作引起癫痫发作是公认的，但进行性癫痫发生的细胞过程仍不清楚。在这里，我们使用光遗传学在体内短暂激活小鼠梨状皮质（PCx）主要神经元的靶向群体。在仅仅3或4天的刺激后，先前的亚惊厥刺激触发了大规模的全身性癫痫发作。高度复发的异皮质特别容易发生“光点燃”。光点燃打破了反复兴奋和反馈抑制的平衡。为了了解这种平衡是如何被破坏的，我们选择性地在体外重新激活相同的神经元。令人惊讶的是，我们没有发现异突触增强的证据，相反，我们观察到一个显着的，路径特异性减少反馈抑制。我们没有发现抑制性中间神经元的损失，相反，反馈抑制性神经元中GABA合成减少似乎是抑制减弱的基础。光点燃将允许精确识别大脑活动模式可以渐进地和病理性地破坏皮质兴奋和抑制平衡的分子过程。Ryu等人使用光遗传学短暂激活小鼠梨状皮质中的主要神经元。4天后，以前无害的刺激引起大规模的全身性癫痫发作。“光点燃”不加强反复兴奋;相反，它通过降低突触间隙GABA浓度和减缓囊泡再填充来减弱反馈抑制，这与GABA合成减少一致。
It is well established that seizures beget seizures, yet the cellular processes that underlie progressive epileptogenesis remain unclear. Here, we use optogenetics to briefly activate targeted populations of mouse piriform cortex (PCx) principal neurons in vivo. After just 3 or 4 days of stimulation, previously subconvulsive stimuli trigger massive, generalized seizures. Highly recurrent allocortices are especially prone to “optokindling.” Optokindling upsets the balance of recurrent excitation and feedback inhibition. To understand how this balance is disrupted, we then selectively reactivate the same neurons in vitro. Surprisingly, we find no evidence of heterosynaptic potentiation; instead, we observe a marked, pathway-specific decrease in feedback inhibition. We find no loss of inhibitory interneurons; rather, decreased GABA synthesis in feedback inhibitory neurons appears to underlie weakened inhibition. Optokindling will allow precise identification of the molecular processes by which brain activity patterns can progressively and pathologically disrupt the balance of cortical excitation and inhibition. Ryu et al. use optogenetics to briefly activate principal neurons in mouse piriform cortex. After 4 days, previously innocuous stimuli evoke massive, generalized seizures. “Optokindling” does not strengthen recurrent excitation; instead, it weakens feedback inhibition by decreasing synaptic cleft GABA concentrations and slowing vesicle refilling, consistent with decreased GABA synthesis.
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