Journal article
Neuregulin 1 transgenic mice display reduced mismatch negativity, contextual fear conditioning and social interactions
Brain research, Vol.1294, pp.116-127
2009
DOI: 10.1016/j.brainres.2009.07.065
PMCID: PMC2771287
PMID: 19643092
Abstract
Neuregulin-1 (
NRG1) is one of susceptibility genes for schizophrenia and plays critical roles in glutamatergic, dopaminergic and GABAergic signaling. Using mutant mice heterozygous for
Nrg1 (
Nrg1
+/−) we studied the effects of Nrg1 signaling on behavioral and electrophysiological measures relevant to schizophrenia.
Behavior of
Nrg1
+/− mice and their wild type littermates was evaluated using pre-pulse inhibition, contextual fear conditioning, novel object recognition, locomotor, and social choice paradigms. Event-related potentials (ERPs) were recorded to assess auditory gating and novel stimulus detection.
Gating of ERPs was unaffected in
Nrg1
+/− mice, but mismatch negativity in response to novel stimuli was attenuated. The
Nrg1
+/− mice exhibited behavioral deficits in contextual fear conditioning and social interactions, while locomotor activity, pre-pulse inhibition and novel object recognition were not impaired.
Nrg1
+/− mice had impairments in a subset of behavioral and electrophysiological tasks relevant to the negative/cognitive symptom domains of schizophrenia that are thought to be influenced by glutamatergic and dopaminergic neurotransmission. These mice are a valuable tool for studying endophenotypes of schizophrenia, but highlight that single genes cannot account for the complex pathophysiology of the disorder.
Details
- Title: Subtitle
- Neuregulin 1 transgenic mice display reduced mismatch negativity, contextual fear conditioning and social interactions
- Creators
- Richard S Ehrlichman - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USASteven N Luminais - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USASamantha L White - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USANoam D Rudnick - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USANan Ma - Department of Biology, University of Pennsylvania, Philadelphia, PA, USAHolly C Dow - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USAArati S Kreibich - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USATed Abel - Department of Biology, University of Pennsylvania, Philadelphia, PA, USAEdward S Brodkin - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USAChang-Gyu Hahn - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USASteven J Siegel - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
- Resource Type
- Journal article
- Publication Details
- Brain research, Vol.1294, pp.116-127
- DOI
- 10.1016/j.brainres.2009.07.065
- PMID
- 19643092
- PMCID
- PMC2771287
- NLM abbreviation
- Brain Res
- ISSN
- 0006-8993
- eISSN
- 1872-6240
- Publisher
- Elsevier BV
- Grant note
- DOI: 10.13039/100000025, name: NIMH, award: P50 MH064045, RO1MH075916, R01MH080718
- Language
- English
- Date published
- 2009
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065835102771
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