17 Poll, Stefanie Mittag, Manuel Musacchio, Fabrizio Justus, Lena C Giovannetti, Eleonora Ambrad Steffen, Julia Wagner, Jens Zohren, Lioba Schoch, Susanne Schmidt, Boris Jackson, Walker S Ehninger, Dan Fuhrmann, Martin AG Fuhrmann AG Jackson AG Ehninger Nature neuroscience Nature neuroscience Nature America New York, NY 1546-1726 10.1038/s41593-020-0652-4 English 952 - 958 8 23 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. PUB:(DE-HGF)16, ; 0, ; Alzheimer Disease: genetics Alzheimer Disease: metabolism Alzheimer Disease: physiopathology Amyloid beta-Protein Precursor: genetics Amyloid beta-Protein Precursor: metabolism Animals Disease Models, Animal Female Hippocampus: physiology Male Mental Recall: physiology Mice Mice, Transgenic Neurons: physiology Optogenetics Proto-Oncogene Proteins c-fos: genetics Proto-Oncogene Proteins c-fos: metabolism Amyloid beta-Protein Precursor Proto-Oncogene Proteins c-fos Journal Article 2020 DZNE-2020-01297 2020 pmid:32514139 https://pub.dzne.de/record/153300 https://doi.org/10.1038/s41593-020-0652-4