INTRODUCTION: N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine are known to induce abnormal high frequency oscillations (HFO; 130-180 Hz) across different rat brain areas. However, the neural mechanisms behind the generation of this rhythm remain poorly understood.

AIM(S): This study aimed to determine the role of the olfactory bulb (OB) in the generation of ketamine-enhanced HFO and whether non-NMDA glutamate receptors, specifically AMPA or kainic acid receptors, contribute to the generation of HFO.

METHOD(S): Adult male Wistar rats were chronically implanted with electrodes and guides in the OB and electrodes in the ventral striatum (VS), prefrontal cortex (PFC), parietal cortex (ECoG-P), and frontal cortex (ECoG-F). Local field potentials were analyzed before and after intraperitoneal injection of ketamine (25 mg/kg). To test the involvement of AMPA/kainate receptors, CNQX/NBQX/UBP310/IEM1925 dihydrobromide (0.5 µg) was infused directly into the OB followed by the systemic administration of ketamine.

RESULTS: Systemic ketamine increased the power of HFO in the OB more strongly than VS or cortical areas (N=19). In a second study (N=7) we found that local OB infusion of CNQX or NBQX significantly reduced ketamine-enhanced HFO power locally and in the VS and PFC. In a third group (N=6) we found OB infusion of a KA antagonist (UBP310) reduced the power of ketamine-enhanced HFO power locally and in VS to a greater extent that the AMPA antagonist (IEM1925).

CONCLUSIONS: Ketamine-enhanced HFO recorded in the VS and PFC is dependent on HFO generated in the OB. Further, within the OB we show that the generation of HFO depends primarily on stimulation of kainate receptors.

FINANCIAL SUPPORT: The authors wish to thank NCN (grant 2021/41/B/NZ4/03882) for funding this project.