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Gap junction networks can generate both ripple-like and fast ripple-like oscillations

Lookup NU author(s): Dr Alistair Jenkins, Professor Roger Whittaker, Dr Ian Schofield, Dr Gavin ClowryORCiD, Professor Mark Cunningham

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Abstract

Fast ripples (FRs) are network oscillations, defined variously as having frequencies of > 150 to > 250 Hz, with a controversial mechanism. FRs appear to indicate a propensity of cortical tissue to originate seizures. Here, we demonstrate field oscillations, at up to 400 Hz, in spontaneously epileptic human cortical tissue in vitro, and present a network model that could explain FRs themselves, and their relation to 'ordinary' (slower) ripples. We performed network simulations with model pyramidal neurons, having axons electrically coupled. Ripples (< 250 Hz) were favored when conduction of action potentials, axon to axon, was reliable. Whereas ripple population activity was periodic, firing of individual axons varied in relative phase. A switch from ripples to FRs took place when an ectopic spike occurred in a cell coupled to another cell, itself multiply coupled to others. Propagation could then start in one direction only, a condition suitable for re-entry. The resulting oscillations were > 250 Hz, were sustained or interrupted, and had little jitter in the firing of individual axons. The form of model FR was similar to spontaneously occurring FRs in excised human epileptic tissue. In vitro, FRs were suppressed by a gap junction blocker. Our data suggest that a given network can produce ripples, FRs, or both, via gap junctions, and that FRs are favored by clusters of axonal gap junctions. If axonal gap junctions indeed occur in epileptic tissue, and are mediated by connexin 26 (recently shown to mediate coupling between immature neocortical pyramidal cells), then this prediction is testable.


Publication metadata

Author(s): Simon A, Traub RD, Vladimirov N, Jenkins A, Nicholson C, Whittaker RG, Schofield I, Clowry GJ, Cunningham MO, Whittington MA

Publication type: Article

Publication status: Published

Journal: European Journal of Neuroscience

Year: 2014

Volume: 39

Issue: 1

Pages: 46-60

Print publication date: 01/01/2014

ISSN (print): 0953-816X

ISSN (electronic): 1460-9568

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/ejn.12386

DOI: 10.1111/ejn.12386


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Funding

Funder referenceFunder name
Alexander von Humboldt Stiftung
Einstein Stiftung Berlin
IBM
Dr Hadwen Trust
MRC Milstein award scheme
Wolfson Foundation
RO1NS044133NIH/NINDS
RO1NS062955NIH/NINDS

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