Fig. 1: Reduced synaptic activity in neurons of patients with two or three copies of the SNCA gene (denoted as 2X and 3X).

A Neurons derived from the 2X patient display reduced excitability compared to controls. Representative evoked potential recordings of a control B, 2X patient C, and 3X patient D. Representative traces of sodium and potassium currents in control individuals E, 2X patient F, and 3X patient G. H Sodium currents of neurons from 3X patient opened at a less depolarized potential than control DA neurons, whereas those derived from the patient with the double copy opened at a more depolarized potential. I Slow potassium currents are reduced in DA neurons derived from 3X patient compared to controls. J Fast potassium currents are reduced in DA neurons derived from 3X patient compared to controls. Example traces of recordings of synaptic currents in DA neurons derived from a control individual K, the 2X patient L, and the 3X patient M. The lower image in each is a zoom of the segment denoted by the black bars in the upper image. N The mean amplitude of synaptic currents is reduced in DA neurons from 2X patient compared to controls. O The average rate of synaptic events is reduced in DA neurons derived from 2X patient and further reduced in 3X patient. P Signaling network analysis with the top enriched KEGG pathways for the 2X patient-derived neurons compared to the controls. Q Signaling network analysis with the top enriched KEGG pathways for the 3X patient-derived neurons compared to the controls. In this figure and the next figures, asterisks represent statistical significance by the following code: *p value < 0.05, **p value < 0.01, ***p < 0.001, ****p < 0.0001. Error bars represent the standard error in this figure and in the next figures unless stated otherwise.