Emergence of dominant initiation sites for interictal spikes in rat neocortex

J Neurophysiol. 2015 Dec;114(6):3315-25. doi: 10.1152/jn.00471.2014. Epub 2015 Oct 7.

Abstract

Neuronal populations with unbalanced inhibition can generate interictal spikes (ISs), where each IS starts from a small initiation site and then spreads activation across a larger area. We used in vivo voltage-sensitive dye imaging to map the initiation site of ISs in rat visual cortex disinhibited by epidural application of bicuculline methiodide. Immediately after the application of bicuculline, the IS initiation sites were widely distributed over the entire disinhibited area. After ∼ 10 min, a small number of sites became "dominant" and initiated the majority of the ISs throughout the course of imaging. Such domination also occurred in cortical slices, which lack long-range connections between the cortex and subcortical structures. This domination of IS initiation sites may allow timing-related plasticity mechanisms to provide a spatial organization where connections projecting outward from the dominant initiation site become strengthened. Understanding the spatiotemporal organization of IS initiation sites may contribute to our understanding of epileptogenesis in its very early stages, because a dominant IS initiation site with strengthened outward connectivity may ultimately develop into a seizure focus.

Keywords: epileptiform focus; interictal spikes; propagating waves; seizure initiation; voltage-sensitive dye imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Animals
  • Bicuculline / pharmacology
  • Convulsants / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Neocortex / drug effects
  • Neocortex / physiology*
  • Neural Inhibition*
  • Rats
  • Rats, Sprague-Dawley
  • Visual Cortex / drug effects
  • Visual Cortex / physiology*

Substances

  • Convulsants
  • Bicuculline