Altered patterning of neural activity in a tauopathy mouse model

Alzheimers 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 animals 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. SignificanceWe expose differences in WT and tau brains, emerging at the circuit level, using a novel, morphological perspective on neural activity. This approach allows identifying qualitative changes in spiking patterns and in extracellular field oscillations, that are not discernible through traditional time-localized or time-averaged analyses. In particular, analyses of activity patterns facilitates detection of neurodegenerative deviations, conspicuously linking their effects to behavior and locomotion, thus opening a new venue for understanding how the architecture of neural activity shifts from normal to pathological.