Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6276810 | Neuroscience | 2010 | 8 Pages |
Abstract
Neuregulin 1 (NRG1), which has been implicated in the development of schizophrenia, is expressed widely throughout the brain and influences key neurodevelopmental processes such as myelination and neuronal migration. The heterozygous transmembrane domain Nrg1 mutant mouse (Nrg1 TM HET) exhibits a neurobehavioural phenotype relevant for schizophrenia research, characterized by the development of locomotor hyperactivity, social withdrawal, increased sensitivity to environmental manipulation, and changes to the serotonergic system. As only limited data are available on the learning and memory performance of Nrg1 TM HET mice, we conducted a comprehensive examination of these mice and their wild type-like littermates in a variety of paradigms, including fear conditioning (FC), radial arm maze (RAM), Y maze, object exploration and passive avoidance (PA). Male neuregulin 1 hypomorphic mice displayed impairments in the novel object recognition and FC tasks, including reduced interest in the novel object and reduced FC to a context, but not a discrete cue. These cognitive deficits were task-specific, as no differences were seen between mutant and control mice in spatial learning (i.e. RAM and Y maze) for both working and reference memory measures, or in the PA paradigm. These findings indicate that neuregulin 1 plays a moderate role in cognition and present further behavioural validation of this genetic mouse model for the schizophrenia candidate gene neuregulin 1.
Keywords
EGFY-mazeDEXN-methyl-d-aspartic acidNRG1NMDAPassive avoidanceSchizophreniagamma-aminobutyric acidanalysis of varianceANOVAlong-term potentiationLTPFear conditioningWorking memoryReference memorystandard error of the meandexamphetamineRamCognitionNovel object recognitionepidermal growth factorSEMMouse modelNORTneuregulin 1Novel Object Recognition taskRadial arm mazeGABA
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Authors
L. Duffy, E. Cappas, D. Lai, A.A. Boucher, T. Karl,