Cortical high-frequency oscillations ({approx} 110 Hz) in cats are state-dependent and enhanced by a subanesthetic dose of ketamine

Abstract

Ketamine is an NMDA receptor antagonist that has both antidepressant and anesthetic properties. At subanesthetic doses, ketamine can cause transient psychosis in humans, and is used to model psychosis in experimental animals. In rodents, subanesthetic doses of ketamine increase the power of high-frequency oscillations (HFO, 100-180 Hz) in the electroencephalogram and field potentials, a frequency band linked to cognitive functions. However, the effects of ketamine in higher mammals, with more translatable relevance, are poorly investigated. Here, we have examined cortical HFO during wakefulness, sleep, and after administering a sub-anesthetic dose of ketamine (15 mg/kg), utilizing the cat as an animal model. Four cats were implanted with cortical electrodes for chronic polysomnographic recordings. HFO power, connectivity, information flow directionality, and their relationships with respiratory activity were analyzed. During wakefulness, but not during sleep, we found that HFO were coupled with the inspiratory phase of the respiration. After ketamine administration, HFO were enhanced significantly and remained associated with the inspiratory phase. The analysis of the information flow after ketamine suggest that HFO originate from the olfactory bulb and stream towards the prefrontal cortex. Accordingly, occluding the nostrils significantly reduced HFO power in both the olfactory bulb and prefrontal cortex. In contrast, auditory stimulation did not affect HFO. In conclusion, spontaneous cortical HFO show certain state-dependent features in cats, and enhancement of this rhythm by ketamine may disrupt cortical information processing, which could contribute to some of the neuropsychiatric manifestations associated with ketamine. HighlightsO_LIKetamine is used to model psychosis in humans and experimental animals C_LIO_LISubanesthetic doses of ketamine increase the power of high-frequency oscillations C_LIO_LIHigh-frequency oscillations are coupled with the inspiratory phase of respiration C_LIO_LIThese oscillations originate in the olfactory bulb and stream to the neocortex C_LIO_LINostril occlusion lowers high-frequency activity in the olfactory bulb and neocortex C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/543142v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@e386feorg.highwire.dtl.DTLVardef@1b3c06aorg.highwire.dtl.DTLVardef@1d93ecorg.highwire.dtl.DTLVardef@1daa161_HPS_FORMAT_FIGEXP M_FIG C_FIG