High-frequency oscillations in the mammalian brain after ketamine and other NMDA receptor antagonists.
Mark Jeremy Hunt, Jacek Wróbel
Journal of Psychopharmacology July 24, 2025 DOI: 10.1177/02698811251352454 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | High-frequency oscillations Nasal respiration Networks Ketamine neuroscience ketamine Antidepressant effects Brain activity Mechanisms Nmda receptor blockade Hfos Lfp signal Powerful rhythms Coherent rhythms |
| Key findings | Ketamine and other NMDAR antagonists markedly enhance high-frequency oscillations (>100 Hz) that are coherent across olfactory and frontostriatal brain regions, driven by respiration-locked olfactory bulb activity. |
Abstract
Subanesthetic doses of ketamine produce complex neuropsychiatric effects, which include rapid psychotomimetic symptoms and antidepressant effects that can last several weeks. Despite over 60 years of research, the mechanism(s) of action underlying ketamine's effects in the brain remains largely mysterious. Neurophysiological field potential recordings provide a direct window into brain activity, with different frequency bands reflecting functionally distinct neural networks. Two decades ago, we reported on the existence of high-frequency oscillations (HFO, >100 Hz) in freely moving rodents that were markedly enhanced by subanesthetic doses of ketamine. Since then, a large body of evidence has shown that HFO after ketamine (and other N-methyl-d-aspartate receptor (NMDAR) antagonists) are largely wake-related and prominent across diverse olfactory and frontostriatal brain regions. This rhythm, which is remarkably coherent across distinct regions, is modulated by slower oscillations with respiration-locked olfactory bulb activity a major driving force behind it. Similar activity has been reported in vivo in a variety of mammals with preclinical validity. This review is the first synthesis of studies reporting on the NMDAR antagonist-enhanced HFO rhythm. We identify current gaps and provide suggestions for future research, including the urgent need for more human studies.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cites 27
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- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways Current Topics in Behavioral Neurosciences 2017
and 22 more in the library