Olfactory bulb circuits drive ketamine-enhanced high-frequency oscillations via kainate and GABAergic mechanisms.

Taisiia Prosvirova; Wiktoria Podolecka; Jacek Wróbel; Mark Jeremy Hunt

doi:10.1016/j.neuropharm.2026.111012

Olfactory bulb circuits drive ketamine-enhanced high-frequency oscillations via kainate and GABAergic mechanisms.

Taisiia Prosvirova, Wiktoria Podolecka, Jacek Wróbel, Mark Jeremy Hunt

Neuropharmacology May 6, 2026 DOI: 10.1016/j.neuropharm.2026.111012 (opens in new tab)

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AI-extracted from the abstract

Characteristics	Experimental study with simultaneous multiregion recordings Peer reviewed
Population	Male Wistar rats
Interventions	Ketamine CNQX NBQX UBP310 IEM-1925 bicuculline
Topics	Ketamine Esketamine
Keywords	Gaba-a receptor Gamma oscillations High-frequency oscillations hfo Kainate receptor Olfactory bulb Rat
Key findings	Ketamine reorganizes fast oscillations across cortical networks by differentially affecting gamma and HFO through dissociable circuit mechanisms involving kainate and GABA-A receptors in the olfactory bulb.

Abstract

Ketamine produces rapid antidepressant effects accompanied by marked changes in fast brain rhythms. High-frequency oscillations (HFO; 130-180 Hz) are an increasingly recognized signature of ketamine across species. However, their relationship to classical gamma activity and their circuit-level organization remain unclear. Using simultaneous multiregion recordings in freely moving male Wistar rats, we show that ketamine differentially reorganizes fast oscillations across cortical networks: neocortical gamma power increased broadly, whereas the olfactory bulb (OB) showed suppressed gamma alongside robust, highly coherent HFO. Local OB infusion of the non-NMDA ionotropic glutamate receptor antagonists CNQX or NBQX suppressed ketamine-enhanced HFO both locally and in ventral striatum and prefrontal cortex without affecting neocortical gamma, indicating dissociable circuit mechanisms. Within the OB, the kainate receptor antagonist UBP310 markedly reduced HFO, whereas AMPA receptor blockade with IEM-1925 had minimal effect. Local GABA-A receptor blockade with bicuculline significantly reduced HFO power while increasing gamma power, demonstrating that intact fast inhibition is required for HFO expression. Based on these findings and known receptor kinetics, we propose that tonic kainate-dependent depolarization recruits interneurons to generate an inhibitory network rhythm, producing synchronized bursts that modulate mitral cell dendrites and drive HFO propagation through olfactory-limbic circuits.

Comparable studies

Other preclinical and animal studies on ketamine, most cited first.

Study	Year	Design
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats	2010	Observational study
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 Conscious rats	1997	Dose-response study with microdialysis and behavioral testing
NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice	2016	Preclinical study
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats	1983	Experimental study
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice	2015	Experimental study

Citations in the library

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