@article {68104,
	title = {Volume-transmitted GABA waves pace epileptiform rhythms in the hippocampal network},
	journal = {Current Biology},
	volume = {33},
	year = {2023},
	month = {2023 Apr 10},
	pages = {1249},
	abstract = {<p>Mechanisms that entrain and drive rhythmic epileptiform discharges remain debated. Traditionally, this quest has been focusing on interneuronal networks driven by GABAergic connections that activate synaptic or extrasynaptic receptors. However, synchronised interneuronal discharges could also trigger a transient elevation of extracellular GABA across the tissue volume, thus raising tonic GABAA\&nbsp;receptor conductance (<em>G</em>tonic) in multiple cells. Here, we use patch-clamp GABA {\textquoteleft}sniffer{\textquoteright} and optical GABA sensor to show that periodic epileptiform discharges are preceded by region-wide, rising waves of extracellular GABA. Neural network simulations that incorporate volume-transmitted GABA signals point to mechanistic principles underpinning this relationship. We validate this hypothesis using simultaneous patch-clamp recordings from multiple nerve cells, selective optogenetic stimulation of fast-spiking interneurons. Critically, we manipulate GABA uptake to suppress extracellular GABA waves but not synaptic GABAergic transmission, which shows a clear effect on rhythm generation. Our findings thus unveil a key role of extrasynaptic, volume-transmitted GABA actions in pacing regenerative rhythmic activity in brain networks.</p>
},
	doi = {10.1016/j.cub.2023.02.051},
	url = {https://doi.org/10.1016/j.cub.2023.02.051},
	author = {Vincent Magloire and Leonid P. Savtchenko and Sergyi Sylantyev and Thomas P. Jensen and Nicholas Cole and Jonathan S. Marvin and Loren L. Looger and Dimitri M. Kullmann and Matthew C. Walker and Ivan Pavlov and Dmitri A. Rusakov}
}
