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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.

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.

SUBMITTER: Hunt MJ

PROVIDER: S-EPMC6300534 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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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.

Hunt Mark Jeremy MJ Adams Natalie E NE Średniawa Władysław W Wójcik Daniel K DK Simon Anna A Kasicki Stefan S Whittington Miles Adrian MA

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180808 2

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 fo ...[more]

PMID: 30140046

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Project description:BackgroundBefore the deposition of amyloid-beta plaques and the onset of learning memory deficits, patients with Alzheimer's disease (AD) experience olfactory dysfunction, typified by a reduced ability to detect, discriminate, and identify odors. Rodent models of AD, such as the Tg2576 and APP/PS1 mice, also display impaired olfaction, accompanied by aberrant in vivo or in vitro gamma rhythms in the olfactory pathway. However, the mechanistic relationships between the electrophysiological, biochemical and behavioral phenomena remain unclear.MethodsTo address the above issues in AD models, we conducted in vivo measurement of local field potential (LFP) with a combination of in vitro electro-olfactogram (EOG), whole-cell patch and field recordings to evaluate oscillatory and synaptic function and pharmacological regulation in the olfactory pathway, particularly in the olfactory bulb (OB). Levels of protein involved in excitation and inhibition of the OB were investigated by western blotting and fluorescence staining, while behavioral studies assessed olfaction and memory function.ResultsLFP measurements demonstrated an increase in gamma oscillations in the OB accompanied by altered olfactory behavior in both APP/PS1 and 3xTg mice at 3-5 months old, i.e. an age before the onset of plaque formation. Fewer olfactory sensory neurons (OSNs) and a reduced EOG contributed to a decrease in the excitatory responses of M/T cells, suggesting a decreased ability of M/T cells to trigger interneuron GABA release indicated by altered paired-pulse ratio (PPR), a presynaptic parameter. Postsynaptically, there was a compensatory increase in levels of GABAAR α1 and β3 subunits and subsequent higher amplitude of inhibitory responses. Strikingly, the GABA uptake inhibitor tiagabine (TGB) ameliorated abnormal gamma oscillations and levels of GABAAR subunits, suggesting a potential therapeutic strategy for early AD symptoms. These findings reveal increased gamma oscillations in the OB as a core indicator prior to onset of AD and uncover mechanisms underlying aberrant gamma activity in the OB.ConclusionsThis study suggests that the concomitant dysfunction of both olfactory behavior and gamma oscillations have important implications for early AD diagnosis: in particular, awareness of aberrant GABAergic signaling mechanisms might both aid diagnosis and suggest therapeutic strategies for olfactory damage in AD.

Dataset Information

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

Publications

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

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