| First Author | Muhia M | Year | 2010 |
| Journal | Eur J Neurosci | Volume | 31 |
| Issue | 3 | Pages | 529-43 |
| PubMed ID | 20105235 | Mgi Jnum | J:159468 |
| Mgi Id | MGI:4443148 | Doi | 10.1111/j.1460-9568.2010.07079.x |
| Citation | Muhia M, et al. (2010) Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP. Eur J Neurosci 31(3):529-43 |
| abstractText | 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. |
