Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP

Mary Muhia, Kay Yan Benjamin Yee, Joram Feldon, Foivos Markopoulos, Irene Knuesel

Research output: Journal article publicationJournal articleAcademic researchpeer-review

47 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)529-543
Number of pages15
JournalEuropean Journal of Neuroscience
Volume31
Issue number3
DOIs
Publication statusPublished - 1 Feb 2010
Externally publishedYes

Keywords

  • Activity
  • Anxiety
  • NMDA receptor
  • Reference memory
  • Working memory

ASJC Scopus subject areas

  • Neuroscience(all)

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