NASAL EPITHELIAL INPUT DRIVES KETAMINE-ENHANCED HIGH- FREQUENCY OSCILLATIONS IN FREELY MOVING RATS

Abstract Background Subanesthetic doses of ketamine are used to model psychoses and for the treatment of depression. The mechanism though which ketamine achieves its effects are not fully understood. Ketamine is known to significantly increase the power of high-frequency oscillations (HFO, 130-180 Hz) in many rodent brain regions. Our previous findings have shown that the olfactory bulb is an important generator of ketamine-enhanced HFO, and may orchestrate this activity in other areas. Aims & Objectives The nasal epithelia houses olfactory sensory neurons whose axons directly innervate the olfactory bulb. Here we tested that the enhancement of HFO, after ketamine, is dependent on input from the nasal epithelia. Method Local field potentials were recorded from the olfactory bulb, ventral striatum and prefrontal cortex of freely moving rats. Damage to the nasal epithelia was induced by intranasal gadolinium infusion. Rats received intraperitoneal ketamine 25 mg/kg injection before and at different time points up to two weeks after nasal infusion. Results Gadolinium nasal infusion, but not saline, was associated with a reduction in respiration rhythm recorded in the olfactory bulb. Ketamine-enhanced HFO power were significantly reduced in all regions we recorded. This effect lasted at least 7 days and was associated with a gradual recovery thereafter. Ketamine-enhanced locomotion was not affected by intranasal gadolinium. Discussion And Conclusion These findings show that ketamine-enhanced HFO in the olfactory bulb, and other brain regions, are dependent on input from the nasal epithelium. The authors wish to thank NCN (grant 2021/41/B/NZ4/03882) for funding this project.