Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7

Gilles Sansig, Trevor J. Bushell, Vernon R.J. Clarke, Andrei Rozov, Nail Burnashev, Chantal Portet, Fabrizio Gasparini, Markus Schmutz, Klaus Klebs, Ryuichi Shigemoto, Peter J. Flor, Rainer Kuhn, Thomas Knoepfel, Markus Schroeder, David R. Hampson, Valerie J. Collett, Congxiao Zhang, Robert M. Duvoisin, Graham L. Collingridge, Herman Van Der Putten

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

To study the role of mGlu7 receptors (mGluR7), we used homologous recombination to generate mice lacking this metabotropic receptor subtype (mGluR7-/-). After the serendipitous discovery of a sensory stimulus-evoked epileptic phenotype, we tested two convulsant drugs, pentylenetetrazole (PTZ) and bicuculline. In animals aged 12 weeks and older, subthreshold doses of these drugs induced seizures in mGluR7-/-, but not in mGluR7+/-, mice. PTZ-induced seizures were inhibited by three standard anticonvulsant drugs, but not by the group III selective mGluR agonist (R,S)-4-phosphonophenylglycine (PPG). Consistent with the lack of signs of epileptic activity in the absence of specific stimuli, mGluR7-/- mice showed no major changes in synaptic properties in two slice preparations. However, slightly increased excitability was evident in hippocampal slices. In addition, there was slower recovery from frequency facilitation in cortical slices, suggesting a role for mGluR7 as a frequency-dependent regulator in presynaptic terminals. Our findings suggest that mGluR7 receptors have a unique role in regulating neuronal excitability and that these receptors may be a novel target for the development of anticonvulsant drugs.

Original languageEnglish (US)
Pages (from-to)8734-8745
Number of pages12
JournalJournal of Neuroscience
Volume21
Issue number22
DOIs
StatePublished - Nov 15 2001

Keywords

  • (R,S)-4-phosphonophenylglycine
  • Epilepsy
  • Group III mGluR
  • Knock-out
  • Mice
  • mGluR7

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Sansig, G., Bushell, T. J., Clarke, V. R. J., Rozov, A., Burnashev, N., Portet, C., Gasparini, F., Schmutz, M., Klebs, K., Shigemoto, R., Flor, P. J., Kuhn, R., Knoepfel, T., Schroeder, M., Hampson, D. R., Collett, V. J., Zhang, C., Duvoisin, R. M., Collingridge, G. L., & Van Der Putten, H. (2001). Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience, 21(22), 8734-8745. https://doi.org/10.1523/jneurosci.21-22-08734.2001