Global excitatory synchrony: Ketamine induces global common-mode excitatory network oscillation by inhibiting key interneurons

Ketamine is a short-acting dissociative anesthetic commonly used in subanesthetic doses for its adjunct analgesic effects or as a treatment for refractory depression. In this study, we use the nematode C. elegans and pan-neuronal GCaMP imaging in 120 head neurons to study the neuronal mechanisms of subanesthetic doses of ketamine, reaching system-wide conclusions about ketamine’s impacts in a small yet complete nervous system. We recorded dynamics across multiple hours of continuous induction periods and subsequent shorter recordings to tease out distinct phases of ketamine-induced states. We identify two distinct anesthetic phases: an early/low dose state of hyperactive synchronized dynamics and late/higher dose state of system disorganization and spasticity of microscale motion. We also examined the individual activity of the NMDA-receptive interneuron AVA. AVA showed activity patterns that were decoupled from the rest of the system. These results are consistent with a hypothesis resulting from human EEG data that ketamine causes disinhibition by the suppression of key inhibitory interneurons. Our results identify functional differences between the low dose activity dynamics and those are higher doses, and demonstrate a mechanism of ketamine in complete nervous systems. [V2] Add statistics code