title: Neuregulin 1 transgenic mice display reduced mismatch negativity, contextual fear conditioning and social interactions.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors: Richard S
authors: RS
authors: Ehrlichman
authors: Steven N
authors: SN
authors: Luminais
authors: Samantha L
authors: SL
authors: White
authors: Noam D
authors: ND
authors: Rudnick
authors: Nan
authors: N
authors: Ma
authors: Holly C
authors: HC
authors: Dow
authors: Arati S
authors: AS
authors: Kreibich
authors: Ted
authors: T
authors: Abel
authors: Edward S
authors: ES
authors: Brodkin
authors: Chang-Gyu
authors: CG
authors: Hahn
authors: Steven J
authors: SJ
authors: Siegel
mesh_terms: D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000502:physiology*; D004777:Environment; D005071:Evoked Potentials; D005239:Fear / Q000502:physiology*; D005260:Female; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D009483:Neuropsychological Tests; D021641:Recognition, Psychology / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia; D012919:Social Behavior
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse