Long-term dynamics of aberrant neuronal activity in awake Alzheimer's disease transgenic mice

To advance our understanding of aberrant neuronal activity in Alzheimer's disease (AD) Korzhova et al. use in vivo two-photon calcium imaging to record activity from cortical neurons of awake APPPS1 transgenic mice over four weeks, during the early phase of plaque deposition. They demonstrate that neuronal network pathology in models of cerebral amyloidosis is the consequence of persistent single cell aberrant neuronal activity, which could have diagnostic and therapeutic relevance for AD. Alzheimer's disease (AD) is associated with aberrant neuronal activity, which is believed to critically determine disease symptoms. How these activity alterations emerge, how stable they are over time, and whether cellular activity dynamics are affected by the amyloid plaque pathology remains incompletely understood. We here repeatedly recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice over four weeks during the early phase of plaque deposition using in vivo two-photon calcium imaging. We found that aberrant activity during this stage largely persisted over the observation time. Novel highly active neurons slowly emerged from former intermediately active neurons. Furthermore, activity fluctuations were independent of plaque proximity, but aberrant activity was more likely to persist close to plaques. These results support the notion that neuronal network pathology observed in models of cerebral amyloidosis is the consequence of persistent single cell aberrant neuronal activity, a finding of potential diagnostic and therapeutic relevance for AD.

Automated summary

The study utilized in vivo two-photon calcium imaging to record the activity of cortical neurons in awake APPPS1 transgenic mice, revealing that persistent single cell aberrant neuronal activity is the cause of neuronal network pathology in cerebral amyloidosis models, which may have diagnostic and therapeutic implications for Alzheimer's disease (AD).