First Author | Poll S | Year | 2020 |
Journal | Nat Neurosci | Volume | 23 |
Issue | 8 | Pages | 952-958 |
PubMed ID | 32514139 | Mgi Jnum | J:298290 |
Mgi Id | MGI:6478736 | Doi | 10.1038/s41593-020-0652-4 |
Citation | Poll S, et al. (2020) Memory trace interference impairs recall in a mouse model of Alzheimer's disease. Nat Neurosci 23(8):952-958 |
abstractText | 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. |