The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2019

The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding.

Résumé

There is a growing consensus that Alzheimer's disease (AD) involves failure of the homeostatic machinery, which underlies the firing stability of neural circuits. What are the culprits leading to neuron firing instability? The amyloid precursor protein (APP) is central to AD pathogenesis, and we recently showed that its intracellular domain (AICD) could modify synaptic signal integration. We now hypothesize that AICD modifies neuron firing activity, thus contributing to the disruption of memory processes. Using cellular, electrophysiological, and behavioral techniques, we show that pathological AICD levels weaken CA1 neuron firing activity through a gene-transcription-dependent mechanism. Furthermore, increased AICD production in hippocampal neurons modifies oscillatory activity, specifically in the γ-frequency range, and disrupts spatial memory task. Collectively, our data suggest that AICD pathological levels, observed in AD mouse models and in human patients, might contribute to progressive neuron homeostatic failure, driving the shift from normal aging to AD.
Fichier principal
Vignette du fichier
islandora_84447.pdf (4.56 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-02341097 , version 1 (18-11-2020)

Identifiants

Citer

Paula Pousinha, Xavier Mouska, Daniela Bianchi, Mariana Temido-Ferreira, Joana Rajão-Saraiva, et al.. The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding.. Cell Reports, 2019, 29 (2), pp.317-331.e5. ⟨10.1016/j.celrep.2019.08.103⟩. ⟨hal-02341097⟩
24 Consultations
28 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More