Fig. 3: Patient-derived hippocampal neurons possessed reduced excitatory post-synaptic activity compared to healthy controls.

Representative evoked action potential traces in (a) control hippocampal neurons and (b) hippocampal PINK1 and PRKN mutant neurons. c The total number of evoked potentials was not significantly different between control and PINK1 and PRKN mutant neurons. Example recordings of EPSCs in (d) control hippocampal neurons and (e) hippocampal PINK1 and PRKN mutant neurons. f The EPSC amplitude was significantly reduced in PINK1 and PRKN mutant neurons compared to control neurons. g Hippocampal PINK1 and PRKN mutant neurons showed significantly reduced EPSC rates compared to control neurons. h The cumulative distribution of EPSC amplitudes showed that EPSC amplitudes of PINK1 and PRKN mutant neurons were left-shifted compared to control neurons, indicating smaller EPSC amplitudes in hippocampal PINK1 and PRKN mutant neurons. A representative trace of the spike shape of (i) control and (j) PINK1 and PRKN mutant neurons. k The 5 ms AHP was not significantly different in PINK1 and PRKN mutant neurons compared to control neurons. Representative recordings of sodium and potassium currents in (l) control neurons and (m) PINK1 and PRKN mutant neurons. n Fast potassium currents and o slow potassium currents were not significantly different in patient-derived hippocampal neurons compared to controls. p Characterization of hippocampal neurons in culture with immunohistochemistry. PROX1 (blue) marks dentate gyrus granule neurons (Scale bar 30 µm). The percentage of PROX1-positive neurons out of the MAP2 positive neurons in immature and mature cultures is shown in Supplementary Fig. 3c and was (73.30 ± 2.49 in control immature neurons and 73.54 ± 5.66 in PINK1 and PRKN mutant immature neurons. In the mature neurons (second time point), the percentage of PROX1-positive neurons was 70.08 ± 2.46 in control mature neurons and 72.86 ± 6.73 in PINK1 and PRKN mutant mature neurons. Asterisks in this figure denote statistical significance as indicated by the following codes: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.