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.

Network and synaptic mechanisms underlying high frequency oscillations in the rat and cat olfactory bulb under ketamine-xylazine anesthesia

“…We found that KX mitral/tufted neurons fire in phase with 80–130 Hz, consistent with a previous finding under KX reporting mitral/tufted firing over 100 Hz and associated with inhalation/exhalation transitions [Burton and Urban, 2014]. Our previous work in freely moving rats given a subanesthetic dose of ketamine also showed spiking phase locked to a fast 130–180 Hz activity [Hunt et al, 2019]. Nasal respiratory therefore provides a gate for the firing of OB projection neurons [Wachowiak, 2011] and the emergence of ketamine-dependent fast rhythms.…”

“…CSD and MUA analyses strongly suggest that mitral/tufted cells are involved in the generation of 80–130 Hz rhythm, consistent with our finding after ketamine in freely moving rats [Hunt et al, 2019]. Excitation, inhibition and gap junctions can all underlie mechanisms of fast oscillatory activity in the brain [Grenier et al, 2001].…”

“…NMDA receptors are important at reciprocal dendrodendritic mitral-granule cell synapses, considered to underlie the generation of fast rhythms in the OB [Neville and Haberly, 2003, Fourcaud-Trocmé et al, 2014, Osinski and Kay, 2016]. We showed recently that the olfactory bulb (OB) is a strong generator of ketamine-dependent HFO in the brain of rodents [Hunt et al, 2019]. The OB appears to have a particularly privileged position since it can impose both fast and slow oscillatory activity in distant regions [Ito et al, 2014].…”

Power and coherence in the EEG of the rat: impact of behavioral states, cortical area, lateralization and light/dark phases

“…Also, as described before (Cavelli et al, 2018), a narrow peak in HFO at ≈ 130 Hz can be appreciated during REM sleep in the OB and sensory cortices (signaled with red arrows in Figure 2). HFO is implicated in the sensory processing (Bauer et al, 2014), and a recent study suggest that the OB is a source of HFO (Hunt et al, 2019). However, the whole HFO band power was not significantly different between NREM and REM sleep, probably because the set of frequencies involved in the peak is much narrower than the whole band.…”

Addressing Pitfalls in Phase-Amplitude Coupling Analysis with an Extended Modulation Index Toolbox

“…Ketamine, a psychoactive compound, has been widely reported to induce abnormal HFO in freely moving rodents (Hunt et al 2006;Cordon et al 2015;Caixeta et al 2013;Pittman-Polletta et al 2018). Recent work suggests the OB is an important generator of this activity, which can impose this activity in ventral striatal areas (Hunt et al 2019). In the OB, it is well-established that theta can couple to gamma oscillations (40-80 Hz) (for review see (Kay 2014)).…”