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 neuronal organization and function and are thought to reflect a component of genetic vulnerability for schizophrenia. We describe differences among inbred mouse strains for ERPs following a novelty detection paradigm, as a model for genetic contributions to disease vulnerability. Auditory-evoked potentials were recorded during an auditory oddball task in nonanesthetized C57BL/6J, C3H/HeJ, and DBA/2J mice prior to and following ketamine (10 mg/kg). Stimuli consisted of 80 sets of 24 standard tones followed by one novel tone. Principal component analysis yielded four temporal components that contribute to the auditory ERP responses to standard and novel stimuli. Two principal components that varied between standard and novel stimuli also differed among inbred mouse strains. Post hoc analyses indicate that strain effects on novelty detection are due to a significant difference between the response to novel and standard tones in C3H/HeJ mice that is absent in the other two strains. Inbred strains of mice vary in their ability to perform neuronal detection of change in the auditory environment. The ability to model novelty detection deficits in mice will aid in identifying genetic contributions to abnormal neuronal organization in people with schizophrenia.

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

“…The response was compared to wt mice during the first 100 ms of each pulse in order to match the known latency of the P1‐N1‐P2 AEP complex in rodents (Siegel et al . 2003, Fejgin et al . 2014, Witten et al .…”

Effects of Chronic Olanzapine and Haloperidol Differ on the Mouse N1 Auditory Evoked Potential

“…The analogous components between the rodent and human are debated (Adler et al, 1986;Ehlers et al, 1997;Miyazato et al, 1999a, b). In mice, Simosky and Stevens consider the mouse N40 to be analogous to the human P50, but we believe that the mouse N40 is analogous to the human N100 (Siegel et al, 2003;Simosky et al, 2003).…”

“…The neurobiology of sensory processing deficits in schizophrenia has been investigated with auditory ERPs in monkeys, cats, rats, and mice, using tasks similar to those used in humans (Boutros et al, 1997;de Bruin et al, 1999;Javitt et al, 2000;Pincze et al, 2001;Siegel et al, 2003;Simosky et al, 2003;Stevens et al, 2001Stevens et al, , 1997. To interpret the findings in these studies, it is important to understand the relationship between auditory evoked components in the species being studied and the analogous components in human.…”

“…These components are also named for latency, P30, N50, and P80 in rats and P20, N40, and P80 in mice (Iwanami et al, 1994;Siegel et al, 2003). The analogous components between the rodent and human are debated (Adler et al, 1986;Ehlers et al, 1997;Miyazato et al, 1999a, b).…”

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

“…Early auditory sensory processing deficits in NR1 mutants S Bickel et al mutant mice was caused by reduced suppression of the response to the second tone (Figure 1). Based on previous studies, we reason that the mouse correlates of the P50 and N100 are the P20 and N40 respectively (named P1 and N1 in this paper) (Umbricht et al, 2004b;Connolly et al, 2004;Siegel et al, 2003). Most gating studies in humans have focused on the P50 component of the human auditory AEP and only few on the N100.…”