--- _id: '2610' abstract: - lang: eng text: 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. acknowledgement: This work was supported in part by the Biotechnology and Biological Sciences Research Council and Medical Research Council (UK). We thank Doris Ruegg for sequencing, Gemma Texido and Klaus Rajewsky for pTV-0 DNA, J.-F. Pin for mGluR8 cDNA, K. von Figura for E14 ES cells, Pedro Grandes for histological examination of brain sections, Christoph Wiessner for help with plots and statistics, Valerie Schuler for help with Western blots, and the team of the Novartis special strain breeding facility for their support. article_processing_charge: No article_type: original author: - first_name: Gilles full_name: Sansig, Gilles last_name: Sansig - first_name: Trevor full_name: Bushell, Trevor last_name: Bushell - first_name: Vernon full_name: Clarke, Vernon last_name: Clarke - first_name: Andrei full_name: Rozov, Andrei last_name: Rozov - first_name: Nail full_name: Burnashev, Nail last_name: Burnashev - first_name: Chantal full_name: Portet, Chantal last_name: Portet - first_name: Fabrizio full_name: Gasparini, Fabrizio last_name: Gasparini - first_name: Markus full_name: Schmutz, Markus last_name: Schmutz - first_name: Klaus full_name: Klebs, Klaus last_name: Klebs - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Peter full_name: Flor, Peter last_name: Flor - first_name: Rainer full_name: Kühn, Rainer last_name: Kühn - first_name: Thomas full_name: Knoepfel, Thomas last_name: Knoepfel - first_name: Markus full_name: Schroeder, Markus last_name: Schroeder - first_name: David full_name: Hampson, David last_name: Hampson - first_name: Valerie full_name: Collett, Valerie last_name: Collett - first_name: Congxiao full_name: Zhang, Congxiao last_name: Zhang - first_name: Robert full_name: Duvoisin, Robert last_name: Duvoisin - first_name: Graham full_name: Collingridge, Graham last_name: Collingridge - first_name: Herman full_name: Van Der Putten, Herman last_name: Van Der Putten citation: ama: 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. doi:10.1523/JNEUROSCI.21-22-08734.2001 apa: 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. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.21-22-08734.2001 chicago: 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. Society for Neuroscience, 2001. https://doi.org/10.1523/JNEUROSCI.21-22-08734.2001. ieee: G. Sansig et al., “Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7,” Journal of Neuroscience, vol. 21, no. 22. Society for Neuroscience, pp. 8734–8745, 2001. ista: 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. mla: 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, doi:10.1523/JNEUROSCI.21-22-08734.2001. short: 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. date_created: 2018-12-11T11:58:39Z date_published: 2001-11-15T00:00:00Z date_updated: 2023-05-24T08:47:53Z day: '15' doi: 10.1523/JNEUROSCI.21-22-08734.2001 extern: '1' external_id: pmid: - '11698585' intvolume: ' 21' issue: '22' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762269/ month: '11' oa: 1 oa_version: Published Version page: 8734 - 8745 pmid: 1 publication: Journal of Neuroscience publication_identifier: issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience publist_id: '4288' quality_controlled: '1' scopus_import: '1' status: public title: Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7 type: journal_article user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17 volume: 21 year: '2001' ...