%0 Journal Article
%A Poll, Stefanie
%A Mittag, Manuel
%A Musacchio, Fabrizio
%A Justus, Lena C
%A Giovannetti, Eleonora Ambrad
%A Steffen, Julia
%A Wagner, Jens
%A Zohren, Lioba
%A Schoch, Susanne
%A Schmidt, Boris
%A Jackson, Walker S
%A Ehninger, Dan
%A Fuhrmann, Martin
%T Memory trace interference impairs recall in a mouse model of Alzheimer's disease.
%J Nature neuroscience
%V 23
%N 8
%@ 1546-1726
%C New York, NY
%I Nature America
%M DZNE-2020-01297
%P 952 - 958
%D 2020
%X In Alzheimer's disease (AD), hippocampus-dependent memories underlie an extensive decline. The neuronal ensemble encoding a memory, termed engram, is partially recapitulated during memory recall. Artificial activation of an engram can restore memory in a mouse model of early AD, but its fate and the factors that render the engram nonfunctional are yet to be revealed. Here, we used repeated two-photon in vivo imaging to analyze fosGFP transgenic mice (which express enhanced GFP under the Fos promoter) performing a hippocampus-dependent memory task. We found that partial reactivation of the CA1 engram during recall is preserved under AD-like conditions. However, we identified a novelty-like ensemble that interfered with the engram and thus compromised recall. Mimicking a novelty-like ensemble in healthy mice was sufficient to affect memory recall. In turn, reducing the novelty-like signal rescued the recall impairment under AD-like conditions. These findings suggest a novel mechanistic process that contributes to the deterioration of memories in AD.
%K Alzheimer Disease: genetics
%K Alzheimer Disease: metabolism
%K Alzheimer Disease: physiopathology
%K Amyloid beta-Protein Precursor: genetics
%K Amyloid beta-Protein Precursor: metabolism
%K Animals
%K Disease Models, Animal
%K Female
%K Hippocampus: physiology
%K Male
%K Mental Recall: physiology
%K Mice
%K Mice, Transgenic
%K Neurons: physiology
%K Optogenetics
%K Proto-Oncogene Proteins c-fos: genetics
%K Proto-Oncogene Proteins c-fos: metabolism
%K Amyloid beta-Protein Precursor (NLM Chemicals)
%K Proto-Oncogene Proteins c-fos (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:32514139
%R 10.1038/s41593-020-0652-4
%U https://pub.dzne.de/record/153300