Effects of strain, novelty, and NMDA blockade on auditory-evoked potentials in mice

Abstract

People with schizophrenia exhibit impaired ability to modify electroencephalographic event-related potential(ERP) responses to novel Stimuli. These deficits serve as a window into the abnormalities of neuronalorganization and function and are thought to reflect acomponent of genetic vulnerability for schizophrenia. We describe differences among inbred mouse strains for ERPs following a noveltydetection paradigm, as a modelfor genetic contributions to disease vulnerability. Auditory-evoked potentials were recorded during anauditory oddballtask in nonanesthetized C57BL/6J, C3H/HeJ, and DBA/2J mice prior to and following ketamine (10 mg/kg). Stimuliconsisted of 80 sets of 24 standard tones followed by one noveltone. Principalcomponent analysis yielded fourtemporalcomponentsthat contribute to the auditory ERP responses to standard and novelstimuli. Two principalcomponents that varied betweenstandard and novelstimulialso differed among inbred mouse strains.Post hocanalyses indicate that strain effects on novelty detectionare due to a significant difference between the response to noveland standard tones in C3H/HeJ mice that is absent in the othertwostrains. Inbred strains of mice vary in their ability to perform neuronaldetection of change in the auditory environment. The ability tomodelnovelty detection deficits in mice willaid in identifying genetic contributions to abnormalneuronalorganization in people withschizophrenia. © 2003 American College of Neuropsychopharmacology.