Genetically engineered MAPT 10+16 mutation causes pathophysiological excitability of human iPSC-derived neurons related to 4R tau-induced dementia

摘要

A Left, DIC image of human iPSC-derived neuronal culture at ~190 DIV showing a patched neuron. Right, statistics of the resting membrane potential (Vrest) of iPSC-derived neurons in control (wild type, wt, tau) line at ~190 and 220 DIV. The two-tailed unpaired t-test indicated. B Statistics of the capacitance (Cm) of iPSC-derived neurons in the control (wt tau) group at different time points. Boxes show median values. Nonparametric Mann–Whitney test indicated. C Left, example of neuron responses (current mode) to a series of hyperpolarizing currents (top); lower panel shows how the membrane constant (τm) was measured. Dotted box, the area for calculating τm (red, linear fit). Right, statistics of the τm value in wt tau neurons at different time points. The two-tailed unpaired t-test indicated. D Same as in (B), but for the input resistance (Rin). The two-tailed unpaired t-test indicated. E Representative recording of changes in membrane potential of an iPSC-derived neuron in response to a hyperpolarizing current (indicated on the top) for the calculation of the voltage drop (Vdrop) and the sag ratio. F Statistical summary for the Vdrop (left) and the sag ratio (right) of control (wt tau) neurons at different time points. The two-tailed unpaired t-test indicated. All data are mean with s.e.m, unless indicated. The number of tested cells shown.