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ePoster
OSCILLATORY SIGNATURES OF ENTORHINAL–HIPPOCAMPAL CIRCUIT-SPECIFIC DISRUPTION IN THE S305N MOUSE MODEL OF EARLY FRONTO-TEMPORAL TAUOPATHY LINKED TO SPATIAL NAVIGATION DEFICITS
Charlie Clarke-Williamsand 8 co-authors
UCL
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS05-09AM-092
Presentation
Date TBA
Board: PS05-09AM-092
Event Information
Poster Board
PS05-09AM-092
Poster
View posterAbstract
Tau pathology is a hallmark of Alzheimer's disease (AD); with the medial entorhinal cortex (mEC) and the hippocampus (Hpc) being amongst the earliest affected by the pathology. Interplay between these regions is well-known to support cognitive abilities related to spatial navigation; in-line with data showing that such detriments are often the earliest seen in individuals who become diagnosed with AD. While such cognitive biomarkers might be able to highlight higher-risk individuals of AD diagnoses, it remains to be elucidated what the neurophysiological signatures of these early perturbations are, their mechanistic underpinnings and how they relate to cognitive impairment. We sought to model this behavioural and neurophysiological phenomenology using the S305N hTauKI mouse-model of early tauopathy: by performing Neuropixels recordings from either mEC or Hpc; combined with a virtual-reality 1D spatial navigation paradigm. S305N mice exhibited clear spatial navigation deficits; which was accompanied by increased frequency of theta oscillations. Using a variety of electrophysiological, computational and molecular methodologies, we reveal coherent evidence supporting a mechanistic hypothesis that this neuropathological signature is driven by sub-circuit-specific disruption within the mEC–Hpc network.
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