Enhanced excitatory synaptic connectivity in layer v pyramidal neurons of chronically injured epileptogenic neocortex in rats

J Neurosci. 2006 May 3;26(18):4891-900. doi: 10.1523/JNEUROSCI.4361-05.2006.

Abstract

Formation of new recurrent excitatory circuits after brain injuries has been hypothesized as a major factor contributing to epileptogenesis. Increases in total axonal length and the density of synaptic boutons are present in layer V pyramidal neurons of chronic partial isolations of rat neocortex, a model of posttraumatic epileptogenesis. To explore the functional consequences of these changes, we used laser-scanning photostimulation combined with whole-cell patch-clamp recording from neurons in layer V of somatosensory cortex to map changes in excitatory synaptic connectivity after injury. Coronal slices were submerged in artificial CSF (23 degrees C) containing 100 microM caged glutamate, APV (2-amino-5-phosphonovaleric acid), and high divalent cation concentration to block polysynaptic responses. Focal uncaging of glutamate, accomplished by switching a pulsed UV laser to give a 200-400 micros light stimulus, evoked single- or multiple-component composite EPSCs. In neurons of the partially isolated cortex, there were significant increases in the fraction of uncaging sites from which EPSCs could be evoked ("hot spots") and a decrease in the mean amplitude of individual elements in the composite EPSC. When plotted along the cortical depth, the changes in EPSCs took place mainly between 150 and 200 microm above and below the somata, suggesting a specific enhancement of recurrent excitatory connectivity among layer V pyramidal neurons of the undercut neocortex. These changes may shift the balance within cortical circuits toward increased synaptic excitation and contribute to epileptogenesis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Analysis of Variance
  • Anesthetics, Local / pharmacology
  • Animals
  • Animals, Newborn
  • Brain Injuries / pathology*
  • Brain Injuries / physiopathology*
  • Brain Mapping
  • Cell Count / methods
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Excitatory Postsynaptic Potentials / radiation effects
  • Glutamates / pharmacology
  • In Vitro Techniques
  • Lysine / analogs & derivatives
  • Lysine / pharmacokinetics
  • Microscopy, Confocal / methods
  • Patch-Clamp Techniques / methods
  • Photic Stimulation / methods
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Somatosensory Cortex / injuries
  • Somatosensory Cortex / pathology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptic Transmission / radiation effects
  • Tetrodotoxin / pharmacology

Substances

  • Anesthetics, Local
  • Excitatory Amino Acid Antagonists
  • Glutamates
  • alpha-(4,5-dimethoxy-2-nitrobenzyl) glutamate
  • Tetrodotoxin
  • 2-Amino-5-phosphonovalerate
  • biocytin
  • Lysine