Hippocampal hyperactivity in a rat model of Alzheimer’s disease

作者：Liudmila Sosulina, Manuel Mittag, Hans‐Rüdiger Geis, Kerstin Hoffmann, Igor V. Klyubin, Yingjie Qi, Julia K. Steffen, Detlef Friedrichs, Niklas Henneberg, Falko Fuhrmann, Daniel Justus, Kevin Keppler, A. Claudio Cuello, Michael J. Rowan, Martin Fuhrmann, Stefan Remy · 发表于：Journal of Neurochemistry · 年份：2021 · DOI：10.1111/jnc.15323 · 被引用次数：54 · 研究领域：Neuroscience and Neuropharmacology Research、Alzheimer's disease research and treatments、Memory and Neural Mechanisms

Abstract Neuronal network dysfunction is a hallmark of Alzheimer's disease (AD). However, the underlying pathomechanisms remain unknown. We analyzed the hippocampal micronetwork in transgenic McGill‐R‐Thy1‐APP rats (APPtg) at the beginning of extracellular amyloid beta (Aβ) deposition. We established two‐photon Ca 2+ ‐imaging in vivo in the hippocampus of rats and found hyperactivity of CA1 neurons. Patch‐clamp recordings in brain slices in vitro revealed increased neuronal input resistance and prolonged action potential width in CA1 pyramidal neurons. We did neither observe changes in synaptic inhibition, nor in excitation. Our data support the view that increased intrinsic excitability of CA1 neurons may precede inhibitory dysfunction at an early stage of Aβ‐deposition and disease progression. image