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Feedforward inhibition contributes to the control of epileptiform propagation speed

Lookup NU author(s): Professor Andrew Trevelyan

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Abstract

It is still poorly understood how epileptiform events can recruit cortical circuits. Moreover, the speed of propagation of epileptiform discharges in vivo and in vitro can vary over several orders of magnitude (0.1-100 mm/s), a range difficult to explain by a single mechanism. We previously showed how epileptiform spread in neocortical slices is opposed by a powerful feedforward inhibition ahead of the ictal wave. When this feedforward inhibition is intact, epileptiform spreads very slowly (∼100 μm/s). We now investigate whether changes in this inhibitory restraint can also explain much faster propagation velocities. We made use of a very characteristic pattern of evolution of ictal activity in the zero magnesium (0 Mg2+) model of epilepsy. With each successive ictal event, the number of preictal inhibitory barrages dropped, and in parallel with this change, the propagation velocity increased. There was a highly significant correlation (p<0.001) between the two measures over a 1000-fold range of velocities, indicating that feedforward inhibition was the prime determinant of the speed of epileptiform propagation. We propose that the speed of propagation is set by the extent of the recruitment steps, which in turn is set by how successfully the feedforward inhibitory restraint contains the excitatory drive. Thus, a single mechanism could account for the wide range of propagation velocities of epileptiform events observed in vitro and in vivo. Copyright © 2007 Society for Neuroscience.


Publication metadata

Author(s): Trevelyan AJ, Sussillo D, Yuste R

Publication type: Article

Publication status: Published

Journal: Journal of Neuroscience

Year: 2007

Volume: 27

Issue: 13

Pages: 3383-3387

ISSN (print): 0270-6474

ISSN (electronic): 1529-2401

Publisher: Society for Neuroscience

URL: http://dx.doi.org/10.1523/JNEUROSCI.0145-07.2007

DOI: 10.1523/JNEUROSCI.0145-07.2007

PubMed id: 17392454


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