Fig. 5: Reduced synaptic activity in neurons derived from an engineered line of iPSCs with an A53T mutation in the SNCA gene compared to isogenic controls.

A No significant change in the excitability of the A53T neurons compared to control neurons. B Example recording of action potentials in current-clamp mode of a control neuron. C Example recording of action potentials in current-clamp mode of an A53T neuron. Sodium currents of A53T neurons open at a lower depolarization potential than control neurons. D Example recording of sodium and potassium currents in voltage-clamp mode in a control neuron. E Example recording of sodium and potassium currents in voltage-clamp mode in an A53T neuron. F No significant changes were observed in the sodium currents of the A53T neurons compared to controls. G No significant changes were observed in the slow potassium currents in the A53T neurons. H No significant changes were observed in the fast potassium currents in the A53T neurons. I The cumulative distribution of the amplitudes of EPSCs is left-shifted in A53T neurons compared to control neurons, indicating lower amplitudes in the A53T neurons. J Representative trace of the synaptic currents in a control neuron (the lower plot presents a zoom-in on the segment denoted in the black dashed lines in the upper graph). K Representative trace of the synaptic currents in an A53T neuron (the lower plot presents a zoom-in on the segment denoted in the black dashed lines in the upper graph). L The average amplitude of synaptic currents was significantly reduced in A53T neurons compared to control neurons. M The average rate of synaptic currents was significantly reduced in A53T neurons compared to the control neurons. N Signaling network analysis with the top enriched KEGG pathways for the A53T mutant compared to the controls.