UC Irvine

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.