An important validation of these cells as model BD neurons is their response to drugs, specifically Li. Our results demonstrate that, similar to our previous report with fibroblast-derived neurons,42 the neurons derived from LR patients responded to Li by decreasing their hyperexcitability but the neurons from the NR group did not (Figures 6a and i). A surprising result was the reduction in the cell capacitance with Li treatment for both the LR and NR neurons (Figures 6h and p). The cell capacitance is proportional to the total area of the membrane, and a reduction may be related to a smaller cell body or fewer branched dendrites/axons. NR neurons have a lower correlation between excitability and capacitance (Supplementary Figures 3o–q), thus despite this decrease in cell capacitance with Li treatment, the NR neurons could be hyperexcitable. The reduced correlation in NR neurons between excitability and cell capacitance may point to some dysregulation between the growth rate of the neuron and ion channel expression in the NR neurons.
