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Hippocampal hyperactivity in a rat model of Alzheimer’s disease
Author(s) -
Sosulina Liudmila,
Mittag Manuel,
Geis HansRüdiger,
Hoffmann Kerstin,
Klyubin Igor,
Qi Yingjie,
Steffen Julia,
Friedrichs Detlef,
Henneberg Niklas,
Fuhrmann Falko,
Justus Daniel,
Keppler Kevin,
Cuello A. Claudio,
Rowan Michael J.,
Fuhrmann Martin,
Remy Stefan
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15323
Subject(s) - hippocampal formation , neuroscience , hippocampus , inhibitory postsynaptic potential , in vivo , genetically modified mouse , extracellular , alzheimer's disease , biology , transgene , disease , medicine , pathology , microbiology and biotechnology , biochemistry , gene
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.