Present address: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Ave, Cambridge, Boston, MA 02138, USA.
Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP
Article first published online: 25 JAN 2010
© The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 31, Issue 3, pages 529–543, February 2010
How to Cite
Muhia, M., Yee, B. K., Feldon, J., Markopoulos, F. and Knuesel, I. (2010), Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP. European Journal of Neuroscience, 31: 529–543. doi: 10.1111/j.1460-9568.2010.07079.x
- Issue published online: 1 FEB 2010
- Article first published online: 25 JAN 2010
- Received 20 March 2009, revised 30 November 2009, accepted 30 November 2009
- NMDA receptor;
- reference memory;
- working memory
The brain-specific Ras/Rap-GTPase activating protein (SynGAP) is a prime candidate linking N-methyl-d-aspartate receptors to the regulation of the ERK/MAP kinase signalling cascade, suggested to be essential for experience-dependent synaptic plasticity. Here, we evaluated the behavioural phenotype of SynGAP heterozygous knockout mice (SG+/−), expressing roughly half the normal levels of SynGAP. In the cognitive domain, SG+/− mice demonstrated severe working and reference memory deficits in the radial arm maze task, a mild impairment early in the transfer test of the water maze task, and a deficiency in spontaneous alternation in an elevated T-maze. In the non-cognitive domain, SG+/− mice were hyperactive in the open field and appeared less anxious in the elevated plus maze test. In contrast, object recognition memory performance was not impaired in SG+/− mice. The reduction in SynGAP thus resulted in multiple behavioural traits suggestive of aberrant cognitive and non-cognitive processes normally mediated by the hippocampus. Immunohistochemical evaluation further revealed a significant reduction in calbindin-positive interneurons in the hippocampus and doublecortin-positive neurons in the dentate gyrus of adult SG+/− mice. Heterozygous constitutive deletion of SynGAP is therefore associated with notable behavioural as well as morphological phenotypes indicative of hippocampal dysfunction. Any suggestion of a possible causal link between them however remains a matter for further investigation.