Emergence of early alterations in network oscillations and functional connectivity in a tau seeding mouse model of Alzheimer's disease pathology

• Published in: Scientific reports Vol. 7; no. 1; pp. 14189 - 14
• Main Authors: Ahnaou, A, Moechars, D, Raeymaekers, L, Biermans, R, Manyakov, N V, Bottelbergs, A, Wintmolders, C, Van Kolen, K, Van De Casteele, T, Kemp, J A, Drinkenburg, W H
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 27.10.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Alzheimer's disease; Animals; Auditory evoked potentials; Cognition; Cognitive ability; Disease Models, Animal; EEG; Electroencephalography; Evoked potentials; gamma-Aminobutyric Acid - metabolism; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - physiopathology; Immunohistochemistry; Information processing; Interneurons; Memory; Mice; Mismatch negativity; Nerve Net - pathology; Nerve Net - physiopathology; Neural networks; Neurodegenerative diseases; Neurons - metabolism; Neurons - pathology; Parvalbumin; Pathology; Prefrontal cortex; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Prefrontal Cortex - physiopathology; Protein seeding; Rodents; Tau protein; tau Proteins - metabolism; Theta rhythms; γ-Aminobutyric acid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-13839-6

Synaptic dysfunction and disconnectivity are core deficits in Alzheimer's disease (AD), preceding clear changes in histopathology and cognitive functioning. Here, the early and late effects of tau pathology induction on functional network connectivity were investigated in P301L mice. Multichannel EEG oscillations were used to compute (1) coherent activity between the prefrontal cortex (PFC) and hippocampus (HPC) CA1-CA3 networks; (2) phase-amplitude cross frequency coupling (PAC) between theta and gamma oscillations, which is instrumental in adequate cognitive functioning; (3) information processing as assessed by auditory evoked potentials and oscillations in the passive oddball mismatch negativity-like (MMN) paradigm. At the end, the density of tau aggregation and GABA parvalbumin (PV+) interneurons were quantified by immunohistochemistry. Early weakening of EEG theta oscillations and coherent activity were revealed between the PFC and HPC CA1 and drastic impairments in theta-gamma oscillations PAC from week 2 onwards, while PV+ interneurons count was not altered. Moreover, the tau pathology disrupted the MMN complex amplitude and evoked gamma oscillations to standard and deviant stimuli suggesting altered memory formation and recall. The induction of intracellular tau aggregation by tau seed injection results in early altered connectivity and strong theta-gamma oscillations uncoupling, which may be exploited as an early electrophysiological signature of dysfunctional neuronal networks.