Destruction of ERP responses to deviance in an auditory oddball paradigm in amyloid infusion mice with memory deficits

Abstract

The amyloid-beta (A beta) oligomer is considered one of the major pathogens responsible for neuronal and synaptic loss in Alzheimer's disease (AD) brains. Although the neurotoxic mechanisms of A beta have been widely investigated, experimental evidence for the direct linkage between neural signaling and cognitive impairments in association with peptide oligomers is lacking. Here, we conducted an auditory oddball paradigm utilizing an A beta-infused Alzheimer's disease mouse model and interpreted the results based on Y-maze behavioral tests. We acutely injected A beta oligomers into the intracerebroventricular brain region of normal mice to induce A beta-associated cognitive impairments. During the auditory oddball paradigm, electroencephalograms (EEG) were recorded from frontal and parietal cortex of A beta-infused and control mice. The event-related potentials (ERPs) elicited by auditory stimuli showed no significant difference in A beta-infused mice compared to control mice. On the other hand, the differential ERP signature elicited by oddball sound stimuli was destructed in the A beta-infused mice group. We noticed that ERP traces to standard and deviant tones were not significantly different in the A beta group, while the control group showed differences in the amplitude of ERP components. In particular, the difference in the first negative component (N1) between standard and deviant tone, which indexes the sensory memory system, was significantly reduced in the parietal cortex of A beta-infused mice. These findings demonstrate the direct influence of A beta oligomers on the functional integrity of cortical areas in vivo. Furthermore, the N1 amplitude difference may provide a potential marker of sensory memory deficits in a mouse model of AD and yield additional targets for drug assessment in AD.