engPoll, StefanieMittag, ManuelJackson, Walker SEhninger, DanFuhrmann, MartinMusacchio, FabrizioJustus, Lena CGiovannetti, Eleonora AmbradSteffen, JuliaWagner, JensZohren, LiobaSchoch, SusanneSchmidt, BorisMemory trace interference impairs recall in a mouse model of Alzheimer's disease.info:eu-repo/classification/ddc/610Alzheimer Disease: geneticsAlzheimer Disease: metabolismAlzheimer Disease: physiopathologyAmyloid beta-Protein Precursor: geneticsAmyloid beta-Protein Precursor: metabolismAnimalsDisease Models, AnimalFemaleHippocampus: physiologyMaleMental Recall: physiologyMiceMice, TransgenicNeurons: physiologyOptogeneticsProto-Oncogene Proteins c-fos: geneticsProto-Oncogene Proteins c-fos: metabolismAmyloid beta-Protein PrecursorProto-Oncogene Proteins c-fosIn 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.Nature neuroscience 23(8), 952 - 958 (2020). doi:10.1038/s41593-020-0652-4info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionNature America2020info:eu-repo/semantics/openAccessinfo:eu-repo/date/embargoEnd/2021-06-08DEhttps://pub.dzne.de/record/153300https://pub.dzne.de/search?p=id:%22DZNE-2020-01297%22Researchersinfo:eu-repo/semantics/altIdentifier/doi/10.60944/dzne-2020-01297info:eu-repo/semantics/altIdentifier/issn/1097-6256info:eu-repo/semantics/altIdentifier/doi/10.1038/s41593-020-0652-4info:eu-repo/semantics/altIdentifier/pmid/pmid:32514139info:eu-repo/semantics/altIdentifier/issn/1546-1726