Feedforward inhibition contributes to the control of epileptiform propagation speed.
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 (approximately 100 microm/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.
Trevelyan
Andrew J
AJ
Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, New York 10027, USA. andytrev@gmail.com
Sussillo
David
D
Yuste
Rafael
R
D000818:Animals; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000503:physiopathology*; D025461:Feedback, Physiological; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000503:physiopathology*