Concomitant deficits in working memory and fear extinction are functionally dissociated from reduced anxiety in metabotropic glutamate receptor 7-deficient mice
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Published Version
Date
2006-06
Authors
Callaerts-Vegh, Zsuzsanna
Beckers, Tom
Ball, Simon M.
Baeyens, Frank
Callaerts, Patrick F.
Cryan, John F.
Molnar, Elek
D’Hooge, Rudi
Journal Title
Journal ISSN
Volume Title
Publisher
Society for Neuroscience
Published Version
Abstract
Metabotropic glutamate receptor 7 (mGluR7), a receptor with a distinct brain distribution and a putative role in anxiety, emotional responding, and spatial working memory, could be an interesting therapeutic target for fear and anxiety disorders. mGluR7-deficient (mGluR7 / ) mice showed essentially normal performance in tests for neuromotor and exploratory activity and passive avoidance learning but prominent anxiolytic behavior in two anxiety tests. They showed a delayed learning curve during the acquisition of the hidden-platform water maze, and three interspersed probe trials indicated that mGluR7 / mice were slower to acquire spatial information. Working memory in the water maze task and the radial arm maze was impaired in mGluR7 / mice compared with mGluR7 / . mGluR7 / mice also displayed a higher resistance to extinction of fear-elicited response suppression in a conditioned emotional
response protocol. In a non-fear-based water maze protocol, mGluR7 / mice displayed similar delayed extinction. These observed behavioral changes are probably not attributable to changes inAMPAorNMDAreceptor function because expression levels of AMPAand NMDA receptors were unaltered. Extinction of conditioned fear is an active and context-dependent form of inhibitory learning and an experimental model for therapeutic fear reduction. It appears to depend on glutamatergic and higher-level brain functions similar to
those involved in spatial working memory but functionally dissociated from those that mediate constitutional responses in anxiety tests.
Description
Keywords
Metabotropic glutamate receptors , Fear and anxiety , Fear extinction , Conditioned emotional response , Learning and memory , Operant
Citation
CALLAERTS-VEGH, Z., BECKERS, T., BALL, S. M., BAEYENS, F., CALLAERTS, P. F., F. CRYAN, J., MOLNAR, E. & D'HOOGE, R. 2006. Concomitant Deficits in Working Memory and Fear Extinction Are Functionally Dissociated from Reduced Anxiety in Metabotropic Glutamate Receptor 7-Deficient Mice. The Journal of Neuroscience, 26, 6573-6582. doi: 10.1523/jneurosci.1497-06.2006