Amyloid and age-induced hippocampal network alterations in the APPswe/PS1dE9 mouse model

Eleonora Ambrad Giovannetti1, Stefanie Poll1, Manuel Mittag1, Falko Fuhrmann1, Julia Steffen1, Prof. Dr. Stefan Remy2, PD. Dr. Martin Fuhrmann1

1 DZNE Bonn
2 LIN Magdeburg

Alzheimer’s disease (AD) is a deleterious condition affecting individuals due to either dominantly transmitted genetic mutations or due to sporadic reasons whose etiology still has to be fully disclosed. Albeit the diversity in mouse models, network alteration is a feature shared by virtually all of them, further underscoring the relevance of this yet poorly understood pathophysiological process. Here, we investigated the effect of amyloidosis on the hippocampal network of the APPswe/PS1dE9 (APP/PS1) mouse model by means of extracellular field recordings and calcium imaging.

Mice were implanted with local field potential electrodes targeting the stratum radiatum of CA1 and tested in an open field test, or implanted with 16 channel linear probes spanning the hippocampus and head-fixed on a linear treadmill. Neural activity was monitored during intervals of quiet but awake state and movement.

Our results show age-dependent alterations in the local field potential spectra of both wild type and APP/PS1 mice, further corroborating the hypothesis that early detection of the pathology through network diagnostic methods can be used as a both a diagnostic and, eventually, a therapeutic tool for the pathology of AD.