Mechanisms of behavioural flexibility in mice - alteration of cognitive demand induced by ageing

Traditionally, behavioural and electrophysiological recordings in animals are performed separately; however their combined use has considerably enriched our understanding of memory-related processes. Especially single unit recordings has paved the way and highlighted performance-specific firing characteristics of neurones in behavioural context and during ageing. Less well explored is the correlation between behavioural activity and global brain activity recorded via EEG, particularly in small rodents. This was largely due to technical limitations of hardware and software and missing features such as time-stamping of events making the mapping of behaviourally relevant global activity complex and lacking precision. This presentation summarises several years of work using EEG recordings from freely moving mice equipped with multichannel wireless microchips (Neurologger – NewBehavior). Devices were validated in multiple behavioural conditions, disease models and in combination with video-observation systems. These include observation of EEG and sleep studies in home cages, in which video-monitored ambulatory activity was compared with accelerometer-based movement detection of the Neurologger. EEG is quantified for vigilance stages, sleep signatures, and stage-specific quantitative EEG power. Longitudinal recordings are presented covering the life-span of mice from 3 – 21 months and highlight the ageing profile and physiological decline. Abnormalities from these EEG signatures are confirmed in studies on genetically or pharmacologically manipulated mice using models for Alzheimer’s disease and schizophrenia to validate EEG as translational biomarker of ageing and declining cognition. A final test explores EEG during behavioural exploration and after neuronal inactivation to validate global EEG changes as biomarkers reflecting behaviour. The synchronisation of video-observation with quantitative cable-free EEG recording provides a major step towards a combined psychophysiological approach desperately needed to improve basic research and translational tools in neurosciences.

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