Memory trace interference impairs recall in a mouse model of Alzheimer’s disease

Published in: Nature Neuroscience, 2020
Type: Journal Article


Stefanie Poll, Manuel Mittag, Fabrizio Musacchio, Lena C. Justus, Eleonora Ambrad Giovannetti, Julia Steffen, Jens Wagner, Lioba Zohren, Susanne Schoch, Boris Schmidt, Walker S. Jackson, Dan Ehninger, and Martin Fuhrmann, "Memory trace interference impairs recall in a mouse model of Alzheimer’s disease" (2020). Nature Neuroscience, Vol. 23(8), p. 952--958


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.


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