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

To address the question whether neuronal activity is altered in awake APPPS1 mice and if so, how stable these aberrant activity levels are, we longitudinally monitored the activity of the same identified neurons in layer 2/3 of the frontal cortex over four consecutive weeks. We performed calcium imaging, using the genetically encoded calcium indicator GCaMP6s^25,26 in awake Amyloid Precursor Protein – Presenilin 1 (APPPS1) transgenic mice²⁷. We measured neural activity in three consecutive imaging sessions, spaced by two weeks (Fig. 1a–c, Supplementary Fig. 1). We started our recordings at the age of 4 months, which in this mouse model represents the early phase of Aβ plaque deposition²⁸. To characterize the cell identity of the imaged neurons, we performed post-hoc immunostainings and found that the vast majority (96.4%) of GCaMP6s expressing cells was, in fact, excitatory…