TY  - JOUR
AU  - Poll, Stefanie
AU  - Mittag, Manuel
AU  - Musacchio, Fabrizio
AU  - Justus, Lena C
AU  - Giovannetti, Eleonora Ambrad
AU  - Steffen, Julia
AU  - Wagner, Jens
AU  - Zohren, Lioba
AU  - Schoch, Susanne
AU  - Schmidt, Boris
AU  - Jackson, Walker S
AU  - Ehninger, Dan
AU  - Fuhrmann, Martin
TI  - Memory trace interference impairs recall in a mouse model of Alzheimer's disease.
JO  - Nature neuroscience
VL  - 23
IS  - 8
SN  - 1546-1726
CY  - New York, NY
PB  - Nature America
M1  - DZNE-2020-01297
SP  - 952 - 958
PY  - 2020
AB  - 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.
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: physiopathology
KW  - Amyloid beta-Protein Precursor: genetics
KW  - Amyloid beta-Protein Precursor: metabolism
KW  - Animals
KW  - Disease Models, Animal
KW  - Female
KW  - Hippocampus: physiology
KW  - Male
KW  - Mental Recall: physiology
KW  - Mice
KW  - Mice, Transgenic
KW  - Neurons: physiology
KW  - Optogenetics
KW  - Proto-Oncogene Proteins c-fos: genetics
KW  - Proto-Oncogene Proteins c-fos: metabolism
KW  - Amyloid beta-Protein Precursor (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-fos (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32514139
DO  - DOI:10.1038/s41593-020-0652-4
UR  - https://pub.dzne.de/record/153300
ER  -