title: The role of group II metabotropic glutamate receptors in cognition and anxiety: comparative studies in GRM2(-/-), GRM3(-/-) and GRM2/3(-/-) knockout mice.
abstract: Group II metabotropic glutamate receptors (mGlu2 and mGlu3, encoded by GRM2 and GRM3) have been implicated in both cognitive and emotional processes, although their precise role remains to be established. Studies with knockout (KO) mice provide an important approach for investigating the role of specific receptor genes in behaviour. In the present series of experiments we extended our prior characterisation of GRM2/3(-/-) double KO mice and, in complementary experiments, investigated the behavioural phenotype of single GRM2(-/-) and GRM3(-/-) mice. We found no consistent effect on anxiety in either the double or single KO mice. The lack of an anxiety phenotype in any of the lines contrasts with the clear anxiolytic effects of mGlu2/3 ligands. Motor co-ordination was impaired in GRM2/3(-/-) mice, but spared in single GRM2(-/-) and GRM3(-/-) mice. Spatial working memory (rewarded alternation) testing on the elevated T-maze revealed a deficit in GRM2(-/-) mice throughout testing, whereas GRM3(-/-) mice exhibited a biphasic effect (initially impaired, but performing better than controls by the end of training). A biphasic effect on activity levels was seen for the GRM2(-/-) mice. Overall, the phenotype in both GRM2(-/-) and GRM3(-/-) mice was less pronounced - if present at all - compared to GRM2/3(-/-) mice, across the range of task domains. This is consistent with possible redundancy of function and/or compensation in the single KO lines. Results are discussed with reference to a possible role for group II metabotropic glutamate receptors at the interface between arousal and behavioural performance, according to an inverted U-shaped function.
authors.affiliation: Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Viale Regina Elena, 299, I-00161 Rome, Italy. Electronic address: bianca.defilippis@iss.it.
authors.forename: Bianca
authors.initials: B
authors.lastname: De Filippis
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Louisa
authors.initials: L
authors.lastname: Lyon
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Tracy
authors.initials: T
authors.lastname: Lane
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Philip W J
authors.initials: PW
authors.lastname: Burnet
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Harrison
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK. Electronic address: david.bannerman@psy.ox.ac.uk.
authors.forename: David M
authors.initials: DM
authors.lastname: Bannerman
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000523:psychology; D003071:Cognition / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*
chemical_list: D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3
keywords: Anxiety; Arousal; Hippocampus; Spatial memory