Flexible Electronics Enable New Insight Into Neuronal Network Dysfunction That Progresses with Aging and Alzheimer's Disease

A major challenge in studying aging processes is that they occur over long time scales and across brain regions, yet they involve changes in individual neurons with millisecond activity. Recent advances in the design of implantable flexible electronics allow them to study the same individual neurons and circuits over multiple months. These properties enable the study of functional changes in brain processes that occur over long periods of time, such as the onset of dementia associated with Alzheimer's disease pathology. In this presentation I will describe the design and use of flexible electronics implanted into the brains of mice that progressively accumulate Alzheimer's disease pathology with age. I will show how flexible electronics enable unique insight into cellular and circuit-level changes over long periods of time. Specifically, two flexible electrophysiology probes with neuron-like design were implanted into a single hemisphere of ThyTau22 or WT mice. One probe was targeted to the hippocampus, and the other to the medial entorhinal cortex. Recordings were made with each probe once per week over 6 months while mice run along a linear track in virtual reality. These data show the progression of an aging and tau-pathology correlated decrease in neuronal network integrity that occurs both within and between the hippocampus and entorhinal cortex at different rates.