---
_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'
fulldoi: https://doi.org/10.1523/JNEUROSCI.21-22-08734.2001
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'
...