Nasal respiration is necessary for ketamine-dependent high frequency network oscillations and behavioral hyperactivity in rats.

Changes in oscillatory activity are widely reported after subanesthetic ketamine, however their mechanisms of generation are unclear. Here, we tested the hypothesis that nasal respiration underlies the emergence of high-frequency oscillations (130-180 Hz, HFO) and behavioral activation after ketamine in freely moving rats. We found ketamine 20 mg/kg provoked "fast" theta sniffing in rodents which correlated with increased locomotor activity and HFO power in the OB. Bursts of ketamine-dependent HFO were coupled to "fast" theta frequency sniffing. Theta coupling of HFO bursts were also found in the prefrontal cortex and ventral striatum which, although of smaller amplitude, were coherent with OB activity. Haloperidol 1 mg/kg pretreatment prevented ketamine-dependent increases in fast sniffing and instead HFO coupling to slower basal respiration. Consistent with ketamine-dependent HFO being driven by nasal respiration, unilateral naris blockade led to an ipsilateral reduction in ketamine-dependent HFO power compared to the control side. Bilateral nares blockade reduced ketamine-induced hyperactivity and HFO power and frequency. These findings suggest that nasal airflow entrains ketamine-dependent HFO in diverse brain regions, and that the OB plays an important role in the broadcast of this rhythm.