Global excitatory synchrony: Ketamine induces global common-mode excitatory network oscillation by decoupling key interneurons.
bioRxiv : the preprint server for biology August 2, 2025 Belen Karakullukcu, Hamilton White, Christopher Connor et al. preprint
Ketamine, a dissociative anesthetic with subanesthetic analgesic and antidepressant properties, alters neuronal signaling in ways not fully understood. Imaging the entire head of the nematode C. elegans during low-dose ketamine induction reveals two distinct phases: an early, low-dose state of hyperactive, synchronized neural activity, and a later, higher-dose state of system disorganization and spastic microscale motion. The NMDA-receptive interneuron AVA decouples from the system under low-dose ketamine. These findings support the hypothesis that ketamine causes neuronal disinhibition by suppressing key inhibitory interneurons, and identify functional differences between low- and high-dose dynamics in a complete nervous system.