Neuregulin 1 Transgenic Mice Display Reduced Mismatch Negativity, Contextual Fear Conditioning and Social Interactions

Brain Res. 2009 Oct 19;1294:116-27. doi: 10.1016/j.brainres.2009.07.065. Epub 2009 Jul 28.

Abstract

Introduction: 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.

Experimental procedure: 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.

Summary: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Auditory Perception / physiology*
  • Brain / physiopathology*
  • Conditioning, Classical / physiology*
  • Environment
  • Evoked Potentials
  • Fear / physiology*
  • Female
  • Locomotion / physiology
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neuregulin-1 / genetics
  • Neuregulin-1 / metabolism*
  • Neuropsychological Tests
  • Recognition, Psychology / physiology
  • Reflex, Startle / physiology
  • Schizophrenia
  • Social Behavior*

Substances

  • Neuregulin-1
  • Nrg1 protein, mouse