Pruning functional connections in human induced pluripotent stem cell derived neural networks

The failure of human neuronal stem cells to integrate with brain tissue suggests the need to provide functional cues to modify and re-organize the existing naive network. Understanding how human neural networks respond to external stimuli is crucial to realizing this goal. Here, we stimulate a human induced pluripotent stem cell (hIPSC)-derived neural network on a microelectrode array in a Hebbian fashion to explore the resulting network changes. Short exposure to our stimulation protocol resulted in rapid de-correlation of prior functional connections as well as the emergence of a few strong negative connections. Furthermore, stimulation of the network increased median firing rates with observed network reorganization maintained over the course of 15 days.