Figure 8: Connectivity reconstruction from neural recordings of developing hiPSC-derived neurons (A) Raster plots of the same MEA well at different time points during development: week 1, 2, 3, and 4 after plating. The four panels shows spiking signals from individual neurons (rows) obtained through spike sorting, PCA and k-means clustering of 300 sec recordings. The culture develops complex network features: from weakly active and randomly organized (individual spiking events), to very active and fully organized (network bursts). (B) Estimated effective connectivity of the developing culture whose activity is described in panel A. Each visual map consists of a 1.2 x 1.2 mm MEA plate (gray area), a 4-by-4 array of micro-electrodes (red circles) and the estimated directed connections (black arrows). The active neurons are represented by black dots; they are randomly distributed around their corresponding sensing electrode within a radius of 50 µm. (C) Directed graph relative to the culture at week 1 and week 4. The connectivity is equivalent to the one visualized in B but, for clarity and consistency with the main text, links between neurons are directed edges (arrows), active neurons are network nodes (blue: connected; yellow: independent). Given a MEA well and a specific time point, indexes refer to active neurons with recorded activity reported in (A). Note, neurons mapped at week 1 do not correspond to neurons mapped in the following weeks, although they are indicated with the same indexes.
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