Extrasynaptic GABA waves underlie epileptiform rhythms in the hippocampal network
biorxiv(2021)
摘要
The cellular and circuit mechanisms that trigger and maintain epileptiform discharges remain the subject of intense debate. We have earlier reported a bell-shape dependence of spiking activity of interneuronal populations on tonic GABAA receptor conductance ( G tonic), suggesting an innate mechanism to enable slow self-sustained network oscillations. In the brain, G tonic is controlled by the slow changes of the extracellular GABA concentration ([GABA]e), which in turn depends on spiking activity of interneurons. Here, we employ outside-out patch-clamp recordings of GABAA receptor and fluorescence imaging of a GABA sensor to show that periodic epileptiform discharges are preceded by [GABA]e rises. Computer simulations of spiking interneuronal networks reveal that incorporating extrasynaptic waves of [GABA]e readily enables periodic occurrences of synchronised interneuronal spiking, which are in phase with rises in G tonic and can trigger short bursts of principal cell spiking. Simultaneous recording from multiple neurons and selective optogenetic stimulation of parvalbumin-positive (PV+) interneurons confirmed the modelling predictions, consistent with a causal relationship between synchronisation of interneuronal activity, inhibitory synaptic input, G tonic, and interictal events. Our findings suggest a key role of [GABA]e dynamics in enabling and pacing regenerative rhythmic activity of brain networks.
### Competing Interest Statement
The authors have declared no competing interest.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要