Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7

G. Sansig, T. Bushell, V. Clarke, A. Rozov, N. Burnashev, C. Portet, F. Gasparini, M. Schmutz, K. Klebs, R. Shigemoto, P. Flor, R. Kühn, T. Knoepfel, M. Schroeder, D. Hampson, V. Collett, C. Zhang, R. Duvoisin, G. Collingridge, H. Van Der Putten, Journal of Neuroscience 21 (2001) 8734–8745.

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Author
Sansig, Gilles; Bushell, Trevor J; Clarke, Vernon R; Rozov, Andrei; Burnashev, Nail A; Portet, Chantal; Gasparini, Fabrizio; Schmutz, Markus; Klebs, Klaus; Shigemoto, RyuichiIST Austria ; Flor, Peter J; Kühn, Rainer
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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.
Publishing Year
Date Published
2001-11-15
Journal Title
Journal of Neuroscience
Volume
21
Issue
22
Page
8734 - 8745
IST-REx-ID

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Sansig G, Bushell T, Clarke V, et al. Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience. 2001;21(22):8734-8745.
Sansig, G., Bushell, T., Clarke, V., Rozov, A., Burnashev, N., Portet, C., … Van Der Putten, H. (2001). Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience, 21(22), 8734–8745.
Sansig, Gilles, Trevor Bushell, Vernon Clarke, Andrei Rozov, Nail Burnashev, Chantal Portet, Fabrizio Gasparini, et al. “Increased Seizure Susceptibility in Mice Lacking Metabotropic Glutamate Receptor 7.” Journal of Neuroscience 21, no. 22 (2001): 8734–45.
G. Sansig et al., “Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7,” Journal of Neuroscience, vol. 21, no. 22, pp. 8734–8745, 2001.
Sansig G, Bushell T, Clarke V, Rozov A, Burnashev N, Portet C, Gasparini F, Schmutz M, Klebs K, Shigemoto R, Flor P, Kühn R, Knoepfel T, Schroeder M, Hampson D, Collett V, Zhang C, Duvoisin R, Collingridge G, Van Der Putten H. 2001. Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience. 21(22), 8734–8745.
Sansig, Gilles, et al. “Increased Seizure Susceptibility in Mice Lacking Metabotropic Glutamate Receptor 7.” Journal of Neuroscience, vol. 21, no. 22, Society for Neuroscience, 2001, pp. 8734–45.

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