Of mice and motion: Behavioural-EEG phenotyping of Alzheimer’s disease mouse models

Abstract

BackgroundRodent electroencephalography (EEG) in preclinical research is frequently conducted in behaving animals. EEG analysis is complicated by a number of confounds, particularly 1. The close relationship between EEG power and movement speed must be controlled for prior to further analysis. 2. The difficulty inherent in identifying EEG epochs associated with a particular behaviour. New MethodWe utilized infra-red event stamping to accurately synchronize EEG recorded superficially above the hippocampus and prefrontal cortex with motion tracking data in a transgenic Alzheimer’s disease (AD) mouse model (PLB1APP) and wild-type controls (PLBWT) performing a Y-maze spontaneous alternation task. Video tracking synchronized epochs capturing specific behaviours were automatically identified and extracted prior to auto-regressive spectral analysis. ResultsDespite comparable behavioural performance, PLB1APP mice demonstrated region and behavioural context specific deficits in regulation of Gamma power: In contrast to controls, hippocampal Gamma response to speed as well as prefrontal activity associated with correct vs. incorrect alternations was absent in PLB1APP mice. Regulation of hippocampal Gamma power in response to direction of movement did not differ. Comparison with existing MethodsThis method allows for the first time to detect behaviour-specific differences in EEG response to speed that can be quantified and actively controlled for. Analysis across multiple parameters engaging different brain regions can now be used for detailed EEG profiling of brain-region specific functions. ConclusionCombining infra-red event-stamping and auto-regressive modelling enables rapid, automated and sensitive phenotyping of AD mouse models. Subtle alterations in brain signalling can be detected prior to overt behavioural impairments.