  Alzheimer's disease (AD) is a complex neurodegenerative condition that
manifests at multiple levels and involves a spectrum of abnormalities ranging
from the cellular to cognitive. Here, we investigate the impact of AD-related
tau-pathology on hippocampal circuits in mice engaged in spatial navigation,
and study changes of neuronal firing and dynamics of extracellular fields.
While most studies are based on analyzing instantaneous or time-averaged
characteristics of neuronal activity, we focus on intermediate timescales --
spike trains and waveforms of oscillatory potentials, which we consider as
single entities. We find that, in healthy mice, spike arrangements and wave
patterns (series of crests or troughs) are coupled to the animal's location,
speed, and acceleration. In contrast, in tau-mice, neural activity is
structurally disarrayed: brainwave cadence is detached from locomotion, spatial
selectivity is lost, the spike flow is scrambled. Importantly, these
alterations start early and accumulate with age, which exposes progressive
disinvolvement the hippocampus circuit in spatial navigation. These features
highlight qualitatively different neurodynamics than the ones provided by
conventional analyses, and are more salient, thus revealing a new level of the
hippocampal circuit disruptions.
