Chronic electrophysiology reveals age related loss of coherence between hippocampus and entorhinal cortex in ThyTau22 mice

Abstract

AbstractBackgroundRecent studies suggest spatial learning and memory impairment, which is an early clinical sign of Alzheimer’s disease (AD), is caused by dysfunction of neurons that communicate between the hippocampus and entorhinal cortex. Technological limitations have prevented chronic cellular‐level tracking of these interconnected brain regions during the many months or years before onset of age‐related cognitive deficits. This study aims to take advantage of recent progress in chronic electrophysiology probes to explore how cellular and circuit‐level changes progress with aging across these two brain regions in a mouse model of AD.MethodTwo flexible electrophysiology probes were implanted with 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 from 32 electrodes from each probe once per week over 6 months while mice were walking along a linear track in virtual reality.ResultLongitudinal electrophysiology in ThyTau22 mice show an aging and tau‐pathology correlated decrease in local field potential (LFP) coherence at multiple frequencies. Decoherence is observed both within and between the hippocampus and entorhinal cortex.ConclusionThese results suggest that tau pathology plays a significant role in the loss of neuronal network integrity with age.