Plasticity of Synaptic Transmission in Human Stem Cell-Derived Neural Networks.

SUMMARY Long-term potentiation and depression, inferred from analysis on brain slices, are considered the cellular processes underlying learning and memory formation. They have not so far been demonstrated in human stem cell-derived neurons. By expressing channelrhodopsin in hESCs-derived glutamate neurons and co-culturing them with GABA neurons, we found that blue light stimulation increased the frequency of mEPSCs and decreased the ratio of PPF in non ChR2-expressing GABA neurons, indicating a facilitating action at the presynaptic terminals. When paired with post-synaptic depolarization, the repetitive stimulation significantly increased the amplitude of light-evoked EPSCs which persisted during the period, indicating LTP. In contrast, low-frequency light stimulation induced LTD. These effects were blocked by NMDA receptor antagonists, suggesting NMDA receptor-mediated synaptic plasticity in human neural networks. Furthermore, Down syndrome patient iPSC-derived neurons showed absence of LTP or LTD. Thus, our platform offers a versatile model for assessing human neural plasticity under physiological and pathological conditions.