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Open Access research with a European policy impact...

The Strathprints institutional repository is a digital archive of University of Strathclyde's Open Access research outputs. Strathprints provides access to thousands of Open Access research papers by Strathclyde researchers, including by researchers from the European Policies Research Centre (EPRC).

EPRC is a leading institute in Europe for comparative research on public policy, with a particular focus on regional development policies. Spanning 30 European countries, EPRC research programmes have a strong emphasis on applied research and knowledge exchange, including the provision of policy advice to EU institutions and national and sub-national government authorities throughout Europe.

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Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7

Sansig, G. and Bushell, T. and Clarke, V.R. and Rozov, A. and Burnashev, N. and Portet, C. and Gasparini, F. and Schmutz, M. and Klebs, K. and Shigemoto, R. and Flor, P.J. and Kuhn, R. and Knoepfel, T. and Schroeder, M. and Hampson, D.R. and Collett, V.J. and Zhang, C. and Duvoisin, R.M. and Collingridge, G.L. and van der Putten, Herman (2001) Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience, 21 (22). pp. 8734-8745. ISSN 0270-6474

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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.