Event-related potentials and pathology in rodent models of Alzheimer's disease and Absence Epilepsy

Electroencephalography (EEG), including the study of event-related potentials (ERPs) and event-related oscillations (EROs), are cost-effective tools in both the clinical practice and in preclinical research field of brain disorders. The electrical activity in the human vs. the rodent’s brain share strong similarities, which make these techniques very attractive from a translational standpoint, but much still needs to be accomplished in order to fully characterize the EEG response as a viable biomarker.We carried out recording experiments in: 1) a wild-type mouse strain; 2) a transgenic mouse regarded as a model of Alzheimer’s disease; 3) a rat model of absence epilepsy; and 4) and inbred mouse spontaneously affected by sleep-related epilepsy. 1) In wild-type C56Bl/6 mice, we tested the sensitivity of auditory event-related potentials (AERPs) and EROs to different manipulations during a passive auditory oddball paradigm. The evoked components showed the same order of polarity described in human and rats, but with shorter latencies, possibly due to the differences in brain size. The P3 component, unlike the earlier components, was sensitive to the probability of stimulus presentation, i.e. it was reduced when the probability of stimulus presentation increased. Also, the EROs associated with the P3 component in mice exhibited similarities with human EROs in terms of evoked power and phase-locking index (PLI). These findings suggest that the P3 component in mice could share features of the human P300, in terms of stimulus processing correlates.2) In TASTPM mice, we analyzed changes in the AERPs, EROs and EEG. An increase in P3 latency and reductions in the amplitudes of N1, P2, and P3 components during target stimulus processing were found in these transgenic mice. Also, these mice exhibited increased delta and theta pre-stimulus activity associated to poor synchronization after the auditory stimulus, connectivity deficits between frontal and parietal sites, and a poor increase of theta total power for the target stimulus. Additionally, specific EEG abnormalities during non-REM sleep characterized by an increase in the power of theta, alpha and beta bands were detected. These findings support the hypothesis that in the TASTPM transgenic model, EEG, AERPs and EROs exhibit anomalies that reflect neural network disturbances typical of AD, and therefore, could be used as biomarkers in transgenic mouse models of AD.3) In WAG/Rij rats, we used electrical evoked potentials to study the interactions between the somatosensorial cortex and different thalamic nuclei, which constitute the cortico-thalamo-cortical system. We detected that the thalamic nuclei that belong to the somatosensorial loop and to the limbic loop have different patterns of electrical evoked responses that are intensity-dependent. In particular, very different responses were detected between the rostral and caudal parts of the thalamic reticular nucleus. These evoked responses reflect the diverse interaction of the hyperexcitable somatosensorial cortex on these circuits and hint the different role of the rostral and caudal parts of the reticular thalamic nucleus in the maintenance of sleep-wave discharges.4) In AJ/JAX mice, we described the sleep-wake architecture and characterized the spike-wave discharges. Our analysis suggest that this strain shows spike-wave discharges and disturbances in the sleep-wake architecture, that are equivalent to the hallmarks reported in patients with absence epilepsy and in genetic rat models. These results highlight the importance of EEG as translatable biomarker in preclinical models. Taken together, these findings strengthen our understanding of the properties of evoked potentials in rodents and support the view that the analysis of EEG signals will prove an invaluable tool, both in the investigation of neurosensory processing mechanisms and as a translational biomarker in studies of neurological diseases.