Insights into neuronal cell death
The study of the mechanisms of cell death in human cortical neurons has been hampered by the lack of human neuronal cultures that exhibit a balanced network of excitatory and inhibitory synapses. Xu et al. now describe a method to culture human neurons with a representative ratio of both excitatory and inhibitory neurons derived from human embryonic stem cells or human inducible pluripotent stem cells. Using this new method, they show that human cortical neurons die in a nitric oxide– and poly(ADP-ribose) polymerase-1–dependent manner. These cultures can be used to study the mechanisms of neurotoxicity in human disorders that involve the demise of cortical neurons.