Selective changes in inhibition as determinants for limited hyperexcitability in the insular cortex of epileptic rats

Eur J Neurosci. 2010 Jun;31(11):2014-23. doi: 10.1111/j.1460-9568.2010.07225.x. Epub 2010 May 24.

Abstract

The insular cortex (IC) is involved in the generalization of epileptic discharges in temporal lobe epilepsy (TLE), whereas seizures originating in the IC can mimic the epileptic phenotype seen in some patients with TLE. However, few studies have addressed the changes occurring in the IC in TLE animal models. Here, we analyzed the immunohistochemical and electrophysiological properties of IC networks in non-epileptic control and pilocarpine-treated epileptic rats. Neurons identified with a neuron-specific nuclear protein antibody showed similar counts in the two types of tissue but parvalbumin- and neuropeptide Y-positive interneurons were significantly decreased (parvalbumin, approximately -35%; neuropeptide Y, approximately -38%; P < 0.01) in the epileptic IC. Non-adapting neurons were seen more frequently in the epileptic IC during intracellular injection of depolarizing current pulses. In addition, single-shock electrical stimuli elicited network-driven epileptiform responses in 87% of epileptic and 22% of non-epileptic control neurons (P < 0.01) but spontaneous postsynaptic potentials had similar amplitude, duration and intervals of occurrence in the two groups. Finally, pharmacologically isolated, GABA(A) receptor-mediated inhibitory postsynaptic potentials had more negative reversal potential (P < 0.01) and higher peak conductance (P < 0.05) in epileptic tissue. These data reveal moderate increased network excitability in the IC of pilocarpine-treated epileptic rats. We propose that this limited degree of hyperexcitability originates from the loss of parvalbumin- and neuropeptide Y-positive interneurons that is compensated by an increased drive for GABA(A) receptor-mediated inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Disease Models, Animal
  • Electrophysiology
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / physiopathology*
  • Humans
  • Interneurons / metabolism
  • Male
  • Muscarinic Agonists / pharmacology
  • Neural Inhibition / physiology*
  • Neuropeptide Y / metabolism
  • Parvalbumins / metabolism
  • Pilocarpine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Transmission / physiology*
  • Temporal Lobe* / anatomy & histology
  • Temporal Lobe* / physiology
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Muscarinic Agonists
  • Neuropeptide Y
  • Parvalbumins
  • Pilocarpine
  • gamma-Aminobutyric Acid