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Propagating Activity in Neocortex, Mediated by Gap Junctions and Modulated by Extracellular Potassium

Lookup NU author(s): Christoforos Papasavvas, Ryley Parrish, Professor Andrew Trevelyan



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Copyright © 2020 Papasavvas et al.Parvalbumin-expressing interneurons in cortical networks are coupled by gap junctions, forming a syncytium that supports propagating epileptiform discharges, induced by 4-aminopyridine. It remains unclear, however, whether these propagating events occur under more natural states, without pharmacological blockade. In particular, we investigated whether propagation also happens when extracellular K+ rises, as is known to occur following intense network activity, such as during seizures. We examined how increasing [K+]o affects the likelihood of propagating activity away from a site of focal (200-400 μm) optogenetic activation of parvalbumin-expressing interneurons. Activity was recorded using a linear 16-electrode array placed along layer V of primary visual cortex. At baseline levels of [K+]o (3.5 mm), induced activity was recorded only within the illuminated area. However, when [K+]o was increased above a threshold level (50th percentile = 8.0 mm; interquartile range = 7.5-9.5 mm), time-locked, fast-spiking unit activity, indicative of parvalbumin-expressing interneuron firing, was also recorded outside the illuminated area, propagating at 59.1 mm/s. The propagating unit activity was unaffected by blockade of GABAergic synaptic transmission, but it was modulated by glutamatergic blockers, and was reduced, and in most cases prevented altogether, by pharmacological blockade of gap junctions, achieved by any of the following three different drugs: quinine, mefloquine, or carbenoxolone. Washout of quinine rapidly re-established the pattern of propagating activity. Computer simulations show qualitative differences between propagating discharges in high [K+]o and 4-aminopyridine, arising from differences in the electrotonic effects of these two manipulations. These interneuronal syncytial interactions are likely to affect the complex electrographic dynamics of seizures, once [K+]o is raised above this threshold level.

Publication metadata

Author(s): Papasavvas CA, Parrish RR, Trevelyan AJ

Publication type: Article

Publication status: Published

Journal: eNeuro

Year: 2020

Volume: 7

Issue: 2

Online publication date: 25/02/2020

Acceptance date: 27/01/2020

Date deposited: 15/04/2020

Publisher: Society for Neuroscience


DOI: 10.1523/ENEURO.0387-19.2020

PubMed id: 32098762


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Funder referenceFunder name
099755/Z/12/ZWellcome Trust
MR/J013250/1Medical Research Council (MRC)