Hippocampal gamma-slow oscillation coupling in macaques during sedation and sleep

Behavioral and neurophysiological evidence suggests that the slow (≤1 Hz) oscillation (SO) during sleep plays a role in consolidating hippocampal (HIPP)-dependent memories. The effects of the SO on HIPP activity have been studied in rodents and cats both during natural sleep and during anesthetic administration titrated to mimic sleep-like slow rhythms. In this study, we sought to document these effects in primates. First, HIPP field potentials were recorded during ketamine-dexmedetomidine sedation and during natural sleep in three rhesus macaques. Sedation produced regionally-specific slow and gamma (∼40 Hz) oscillations with strong coupling between the SO phase and gamma amplitude. These same features were seen in slow-wave sleep (SWS), but the coupling was weaker and the coupled gamma oscillation had a higher frequency (∼70 Hz) during SWS. Second, electrical stimuli were delivered to HIPP afferents in the parahippocampal gyrus (PHG) during sedation to assess the effects of sleep-like SO on excitability. Gamma bursts after the peak of SO cycles corresponded to periods of increased gain of monosynaptic connections between the PHG and HIPP. However, the two PHG-HIPP connectivity gains during sedation were both substantially lower than when the animal was awake. We conclude that the SO is correlated with rhythmic excitation and inhibition of the PHG-HIPP network, modulating connectivity and gamma generators intrinsic to this network. Ketamine-dexmedetomidine sedation produces a similar effect, but with a decreased contribution of the PHG to HIPP activity and gamma generation.