Altered patterning of neural activity in a neuropathology

The dynamics of neural circuits and their role in mediating cellular and organismal phenomena remain poorly understood, despite numerous efforts to dissect these processes through precise instantaneous measurements or longer-time averages and approximations. We use an alternative approach: we investigate these dynamics at the system's mesoscale by analyzing spike trains and waveforms. These extended activity patterns carry robust, tractable information, are highly responsive to physiological specifics, and enable detailed tracking of circuit behavior. In particular, this methodology allows for characterizing the functionality of tau-pathology-afflicted hippocampal circuits and identifying circuit-level abnormalities that are missed by through traditional analyses. In healthy mice, spike flows and field undulations exhibit strong coupling with the animal's location, speed, and acceleration. In contrast, neural activity in tau-mice is profoundly disorganized: brainwave cadence becomes decoupled from locomotion, spatial selectivity is lost, and spike flow is disrupted. Importantly, these alterations emerge early and progressively worsen with age, revealing a gradual dissociation of the hippocampal circuit from spatial behavior.