Neuronal Population Effects of Ketamine on Human Brain Organoids
bioRxiv (Cold Spring Harbor Laboratory) March 10, 2026 Arina Nikitina, Christian Bustamante Toro, Raymond Gifford et al.
Ketamine rapidly silences population bursting in human forebrain organoids by disconnecting a subset of 'backbone' neurons that normally drive network activity, while individual neuron firing continues mostly unchanged. Acute exposure to 20 μg/mL ketamine abolished population bursts, reduced mean firing rates, and decreased functional connectivity globally, with backbone units losing their normally elevated connectivity. Re-exposure after chronic treatment no longer silenced bursting, indicating tolerance, though the network remained less active and less connected with fewer backbone units. The organoid-microelectrode array platform offers a scalable human-relevant system for studying circuit-level drug effects.