Global excitatory synchrony: Ketamine induces global common-mode excitatory network oscillation by decoupling key interneurons.
Belen Karakullukcu, Hamilton White, Christopher Connor, Christopher Gabel
bioRxiv : the preprint server for biology August 2, 2025 preprint DOI: 10.1101/2025.08.02.667727 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | C. elegans nematodes |
| Intervention | Ketamine |
| Dose | low dose ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Anesthesia C. elegans Induction Neural activity Dispim |
| Key findings | Low-dose ketamine induces hyperactive synchronized neural activity followed by system disorganization at higher doses, with the NMDA-receptive interneuron AVA decoupling from the network. |
Abstract
Ketamine is a dissociative anesthetic used in subanesthetic doses with analgesic and anti-depressive properties. However, its mechanistic effects on neuronal signaling and circuit function remain underexplored. We address this shortcoming by employing multi-neuronal imaging in the simple nematode C. elegans that allows measurement of neuron activity across the animal's entire head with single-cell resolution. Neuronal imaging during low dose ketamine induction reveals two distinct phases: an early/low dose state of hyperactive synchronized dynamics and late/higher dose state of system disorganization and spastic microscale motion. Specifically examining the activity of the NMDA-receptive interneuron AVA, we find it decouples from the system under low dose ketamine. These results are consistent with the clinical hypothesis that ketamine causes neuronal disinhibition through suppression of key inhibitory interneurons. We identify functional differences between low and high dose activity dynamics and elucidate a mechanism of action of ketamine in a complete, intact nervous system.
Comparable studies
Other experimental studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals | 1995 | Experimental study | |
| The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants | 2019 | Controlled experimental study | n = 15 |
| Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects | 2003 | Experimental study | n = 7 |
| Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants | 2015 | Experimental study | |
| Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression | 2012 | Population pharmacokinetic analysis | n = 9 |
Citations in the library
Cites 5
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
- Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors. Proceedings of the National Academy of Sciences May 28, 2024