Altered dorsal CA1 neuronal population coding in the APP/PS1 mouse model of Alzheimer’s disease

To study the effect of amyloid pathology on network activity in awake animals, high-density 128 channel arrays were targeted to the dCA1 region in head-fixed APP/PS1 and littermate non-transgenic control mice (n = 4 male APP/PS1, n = 4 male control, age = 11–13 months) trained to run freely on a one-dimensional wheel. A representative example of band passed (500–3500 Hz) voltage traces for 4 of the 128 channels in a control (Fig. 1a) and an APP/PS1 mouse (Fig. 1j) reveal spiking activity from multiple neurons. From the raw traces, we identified spike waveforms for individual representative units on a single probe shank for a control (Fig. 1b) and APP/PS1 (Fig. 1k) by concatenating putative spikes across neighboring channels, projecting the concatenated waveforms onto a low-dimensional space using principal components analysis (PCA), and identifying clusters…