C.P. and T.A. authors contributed equally to this study.
Excessive novelty-induced c-Fos expression and altered neurogenesis in the hippocampus of GluA1 knockout mice
Version of Record online: 14 NOV 2010
© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 33, Issue 1, pages 161–174, January 2011
How to Cite
Procaccini, C., Aitta-aho, T., Jaako-Movits, K., Zharkovsky, A., Panhelainen, A., Sprengel, R., Linden, A.-M. and Korpi, E. R. (2011), Excessive novelty-induced c-Fos expression and altered neurogenesis in the hippocampus of GluA1 knockout mice. European Journal of Neuroscience, 33: 161–174. doi: 10.1111/j.1460-9568.2010.07485.x
- Issue online: 4 JAN 2011
- Version of Record online: 14 NOV 2010
- Received 9 June 2010, revised 21 September 2010, accepted 24 September 2010
- AMPA receptors;
- dentate gyrus;
- immediate-early gene
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit-deficient (GluA1−/−) mice display novelty-induced hyperactivity, cognitive and social defects and may model psychiatric disorders, such as schizophrenia and depression/mania. We used c-Fos expression in GluA1−/− mice to identify brain regions responsible for novelty-induced hyperlocomotion. Exposure to a novel cage for 2 h significantly increased c-Fos expression in many brain regions in both wild-type and knockout mice. Interestingly, the clearest genotype effect was observed in the hippocampus and its main input region, the entorhinal cortex, where the novelty-induced c-Fos expression was more strongly enhanced in GluA1−/− mice. Their novelty-induced hyperlocomotion partly depended on the activity of AMPA receptors, as it was diminished by the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulphonamide (NBQX) and unaffected by the AMPA receptor potentiator 2,3-dihydro-1,4-benzodioxin-6-yl-1-piperidinylmethanone (CX546). The hyperlocomotion of GluA1−/− mice was normalised to the level of wild-type mice within 5–6 h, after which their locomotion followed normal circadian rhythm and was not affected by acute or chronic treatments with the selective serotonin reuptake inhibitor escitalopram. We propose that hippocampal dysfunction, as evidenced by the excessive c-Fos response to novelty, is the major contributor to novelty-induced hyperlocomotion in GluA1−/− mice. Hippocampal dysfunction was also indicated by changes in proliferation and survival of adult-born dentate gyrus cells in the knockout mice. These results suggest focusing on the functions of hippocampal formation, such as novelty detection, when using the GluA1−/− mouse line as a model for neuropsychiatric and cognitive disorders.