Neuregulin 1 transgenic mice display reduced mismatch negativity, contextual fear conditioning and social interactions.
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.
Ehrlichman
Richard S
RS
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Luminais
Steven N
SN
White
Samantha L
SL
Rudnick
Noam D
ND
Ma
Nan
N
Dow
Holly C
HC
Kreibich
Arati S
AS
Abel
Ted
T
Brodkin
Edward S
ES
Hahn
Chang-Gyu
CG
Siegel
Steven J
SJ
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
D020890:Neuregulin-1; C490581:Nrg1 protein, mouse