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Asynchronous GABA release at output synapses of fast-spiking interneurons shortens the duration of network activity

Asynchronous GABA release at output synapses of fast-spiking...

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中国神经科学学会第十二届全国学术会议

作者： Quan-Sheng He Da-Hui Wang You-Sheng Shu School of Brain and Cognitive Sciences Beijing Normal University Institute of Systems Science Beijing Normal University

The release of neurotransmitter is normally synchronized to the presynaptic action potential（AP）, however at certain types of synapses neurotransmitter release is not tightly coupled to APs, showing delayed, prolonged and thus asynchronous release（AR）. Output synapses of cortical fast-spiking（FS） interneurons show both synchronous release（SR） and AR, and the strength of AR is substantially enhanced in epileptic tissue. The underlying mechanism of AR and its role in regulating network activity remains unclear. We performed whole-cell recording from FS cells and their neighboring pyramidal cells（PC） in rodent and human cortical slices. High frequency stimulation in FS cells could cause AR at FS autapses and FS-to-PC synapses. During the stimulation, the number of AR progressively built up, and the SR gradually decreased, while the total amount of release kept relatively constant. Immediately after the stimulation, the number of AR showed an abrupt increase and then decayed exponentially. These data suggest that AR competes with SR for the same pool of vesicles, but uses different release machinery. To address the functional role of AR in regulating network activity, we built a computational network model where excitatory PCs and FS cells showed recurrent synaptic connections and FS cells possessed autaptic connections. This model captured our experimental observations and could generate network activity. Enhancing the AR strength shortened the duration of network activity but had no effect on the propagation velocity. Together, our results support the vesicle-completing mechanism of AR and suggest an important role of AR in shaping network activity, which might alleviate epileptiform activities in human patients.

关键词： Asynchronous release vesicle competing GABA epilepsy cerebral cortex

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