Memory trace interference impairs recall in a mouse model of Alzheimer’s disease
- 8 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 23 (8), 952-958
- https://doi.org/10.1038/s41593-020-0652-4
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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (SFB 1089 C01 and B06, SFB 1089 C01)
- Centers of excellence in Neurodegeneration (CoEN 3018)ERA-NET Neuron
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