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

Nature Neuroscience
Stefanie PollMartin Fuhrmann

Abstract

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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Citations

Sep 17, 2020·Cerebral Cortex·Satoshi Iwasaki, Yuji Ikegaya
Jul 2, 2020·Nature Neuroscience·Ryang KimTakashi Kitamura
Mar 2, 2021·Neurobiology of Aging·Kubra Gulmez KaracaAna M M Oliveira
Apr 4, 2021·Current Opinion in Neurobiology·Tomás J RyanSiddhartha Sen
Jun 27, 2021·Hippocampus·Gabriel Berdugo-VegaFederico Calegari
Jul 10, 2021·Neuron·André F de SousaAlcino J Silva
Jan 15, 2022·Nature Reviews. Neuroscience·Tomás J Ryan, Paul W Frankland

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Software Mentioned

GraphPad Prism
ThorImageLS
Fiji ImageJ
CaImAn
ImageJ
GraphPad
OASIS
Fiji
EthoVision XT
TurboReg

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