A. SMN knockdown in iPSC motor neurons was validated by western blot (n=3). Analyzed by t-test, **p=0.0087 B. Control and SMN knock down motor neurons were exposed for 24 h to conditioned media. Representative images of each group were taken. Yellow arrow indicates the motor neuron that was patched. White arrow denotes glass capillary used for recording and to inject dye for visualization. Scale bar = 50 μm. C. Number of action potentials was recorded in control motor neurons (control motor neuron media n=15, control microglia media n=16, and SMA iPSC derived microglia conditioned media n=8). ** p=0.0053. D. Inward sodium current was recorded in control motor neurons exposed 24 h to conditioned media (control motor neuron media n=15, control microglia media n=16, and SMA microglia media n=6). E. Outward potassium current was recorded in control motor neurons exposed for 24 h to conditioned media (control motor neuron media n=8, control microglia media n=9, and SMA microglia media n=9). F. Number of action potentials were recorded in SMN knock down motor neurons (control motor neuron media n=10, control microglia media n=13, and SMA microglia media n=13). ** p=0.0026. G. Inward sodium current was recorded in SMN knock down motor neurons exposed to conditioned media for 24 h (control motor neuron media n=10, control microglia media n=12, and SMA iPSC derived microglia conditioned media n=13). * p=0.0205 H. Outward potassium current was recorded in SMN knockdown motor neurons exposed 24 h to conditioned media (control motor neuron media n=10, control microglia media n=13, and SMA microglia media n=13). * p=0.0213 ** p=0.0034. All groups analyzed by one-way ANOVA. Values represent mean ±SEM.