Inhibitory neurons are critical for normal brain function but dysregulated in disorders such as epilepsy. At least two theories exist for how inhibition may acutely decrease during a seizure: hyperpolarization of fast-spiking (FS) inhibitory neurons by other inhibitory neurons, or depolarization block (DB) of FS neurons resulting in an inability to fire action potentials. Firing rate alone is unable to disambiguate these alternatives. Here, we show that human FS neurons can stop firing due to both hyperpolarization and DB within the same seizure. However, only DB of FS cells is associated with dramatic increases in local seizure amplitude, unobstructed traveling waves, and transient increases in excitatory neuronal firing. This result is independent of seizure etiology or focus. Computational models of DB reproduce the in vivo human biophysics. These methods enable intracellular decoding using only extracellular recordings in humans and explain the otherwise ambiguous inhibitory neuronal control of human seizures.

中文翻译：

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抑制性神经元关闭的两种模式可明显放大人类的癫痫发作

抑制性神经元对于正常的大脑功能至关重要，但在癫痫等疾病中却失调。对于癫痫发作期间抑制作用如何急剧减少，存在至少两种理论：快速抑制（FS）抑制神经元被其他抑制神经元超极化，或FS神经元的去极化阻滞（DB）导致无法激发动作电位。单凭射击率就无法消除这些选择的歧义。在这里，我们显示人类FS神经元可以在同一次发作中由于超极化和DB而停止放电。但是，只有FS细胞的DB与局部癫痫发作幅度的急剧增加，行进波的通畅以及兴奋性神经元放电的短暂增加有关。该结果与癫痫病因或病灶无关。DB的计算模型重现了体内人类生物物理学。