NMDA receptor-mediated excitability in dendritically deformed dentate granule cells in pilocarpine-treated rats

Neurosci Lett. 1991 Aug 5;129(1):69-73. doi: 10.1016/0304-3940(91)90722-6.

Abstract

Membrane properties and synaptic responses were analyzed in dentate granule cells in hippocampal slices prepared from pilocarpine-treated, chronically epileptic rats. Perforant path stimulation evoked a long-lasting excitatory postsynaptic potential (EPSP) with multiple spikes in a stimulus intensity-dependent fashion. The response was strongly facilitated by paired-pulse stimulation. Application of N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovalerate (APV), not only blocked the paired pulse facilitation but also reduced the amplitude of the EPSP, indicating the involvement of the NMDA-receptor in synaptic responses of pilocarpine-treated dentate granule cells. Dendrites of these neurons showed loss of spines and beaded branches. These findings suggest that a degenerating dendrite could be a morphological substrate of neuronal hyperexcitability mediated by NMDA receptors, implicating possible in vivo glutamate toxicity as an underlying mechanism of chronic epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Dendrites / physiology*
  • Epilepsy / etiology
  • Glutamates / toxicity
  • Glutamic Acid
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Pilocarpine / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synaptic Transmission

Substances

  • Glutamates
  • Receptors, N-Methyl-D-Aspartate
  • Pilocarpine
  • Glutamic Acid
  • 2-Amino-5-phosphonovalerate