Vulnerability of short-term memory in a mouse model of Alzheimer’s disease

TL;DR

This study shows that a mouse model of Alzheimer’s disease has weakened short-term memory due to disrupted brain communication.

Contribution

The study identifies reduced functional connectivity and impaired spatiotemporal degeneracy as key mechanisms of short-term memory deficits in Alzheimer’s disease.

Findings

APP-KI mice show increased susceptibility of short-term memory to sensory perturbations.

Reduced spatiotemporal degeneracy in the dorsal cortex explains attenuated robustness during sensorimotor transformations in AD models.

Abstract

Interference from distracting stimuli renders short-term memory vulnerable. While behavioral evidence suggests short-term memory deficits in Alzheimer’s disease (AD), the underlying neural mechanisms remain poorly understood. Using a mouse model of AD (APP-KI), we identified increased susceptibility of short-term memory to sensory perturbations. Simultaneous two-photon calcium imaging across eight cortical regions during a delayed-response task showed that distractors disrupted neural selectivity at both single-neuron and population levels in APP-KI mice. Recurrent neural network models replicating the neural activity of APP-KI mice exhibited decreased stability, consistent with reduced functional connectivity across the dorsal cortex. Furthermore, analyses of multi-regional corticocortical communication revealed reduced spatiotemporal degeneracy in activity transmission within the dorsal cortex of APP-KI mice, which could account for their attenuated robustness during sensorimotor transformations. Collectively, these findings identify reduced functional connectivity and impaired spatiotemporal degeneracy as central mechanisms of short-term memory deficits in the APP-KI mouse model of AD.

In this study, the authors reveal that short-term memory is more vulnerable in a mouse model of Alzheimer’s disease, with experimental and theoretical analyses revealing weakened, less redundant inter-cortical communication that destabilizes short-term memory.

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