A new study from the Makino Group has been published in Nature Communications.
Short-term memory is easily affected by distracting stimuli in the surrounding environment. In Alzheimer’s disease (AD), behavioral studies have suggested declines in short-term memory, but the underlying neural mechanisms remain unclear. In this study, we used an AD model mouse (APP-KI) and found that short-term memory becomes more vulnerable to sensory distractions.
Using two-photon calcium imaging to simultaneously observe eight cortical regions during a delayed-response task, we found that in APP-KI mice, distracting stimuli disrupted neural selectivity—from single neurons to neural populations—regarding which information they respond to. In addition, recurrent neural network models that reproduced the neural activity of APP-KI mice showed decreased network stability, consistent with reduced functional connectivity across the dorsal cortex.
Furthermore, analyses of information transmission across multiple cortical regions revealed that APP-KI mice exhibited reduced “spatiotemporal degeneracy,” or the diversity of activity patterns, within the dorsal cortex. This reduction may contribute to decreased robustness in transforming sensory information into motor responses.
Taken together, these findings indicate that reduced functional connectivity and impaired spatiotemporal degeneracy play central roles in short-term memory deficits in the APP-KI Alzheimer’s disease model.
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Nature Communications : https://doi.org/10.1038/s41467-026-69619-2
