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The olfactory bulb is a source of high-frequency oscillations (130-180 Hz) associated with a subanesthetic dose of ketamine in rodents.

Mark Jeremy Hunt, Natalie E Adams, Władysław Średniawa, Daniel K Wójcik, Anna Simon, Stefan Kasicki, Miles Adrian Whittington

Neuropsychopharmacology January 2019 DOI: 10.1038/s41386-018-0173-y (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical experimental study Peer reviewed
Population Male Wistar rats
Intervention Ketamine
Dose subanesthetic dose
Topics Esketamine Ketamine
Key findings The authors argue that the olfactory bulb is a source of ketamine-induced high-frequency oscillations (130-180 Hz) that can contribute to oscillations in the ventral striatum. Ketamine-HFO was larger and phase-advanced in the olfactory bulb, Granger causality supported the bulb as source, and naris blockade or local inhibition attenuated HFO locally and in ventral striatum; mitral/tufted cell firing was phase-locked to HFO.

Abstract

High-frequency neuronal population oscillations (HFO, 130-180 Hz) are robustly potentiated by subanesthetic doses of ketamine. This frequency band has been recorded in functionally and neuroanatomically diverse cortical and subcortical regions, notably ventral striatal areas. However, the locus of generation remains largely unknown. There is compelling evidence that olfactory regions can drive oscillations in distant areas. Here we tested the hypothesis that the olfactory bulb (OB) is a locus for the generation of HFO following a subanesthetic dose of ketamine. The effect of ketamine on the electrophysiological activity of the OB and ventral striatum of male Wistar rats was examined using field potential and unit recordings, local inhibition, naris blockade, current source density and causality estimates. Ketamine-HFO was of larger magnitude and was phase-advanced in the OB relative to ventral striatum. Granger causality analysis was consistent with the OB as the source of HFO. Unilateral local inhibition of the OB and naris blockade both attenuated HFO recorded locally and in the ventral striatum. Within the OB, current source density analysis revealed HFO current dipoles close to the mitral layer and unit firing of mitral/tufted cells was phase locked to HFO. Our results reveal the OB as a source of ketamine-HFO which can contribute to HFO in the ventral striatum, known to project diffusely to many other brain regions. These findings provide a new conceptual understanding on how changes in olfactory system function may have implications for neurological disorders involving NMDA receptor dysfunction such as schizophrenia and depression.

Comparable studies

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

Study Year Design Participants
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

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