Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the...

An explosion of recent findings firmly demonstrated that brain activity and cognitive function in rodents and humans are modulated synchronously with nasal respiration. Rhythmic respiratory (RR) coupling of wide-spread forebrain activity was confirmed using advanced techniques, including current source density analysis, single unit firing, and phase modulation of local gamma activity, creating solid premise for investigating how higher networks use this mechanism in their communication. Here we show essential differences in the way prefrontal cortex (PFC) and hippocampus (HC) process the RR signal from the olfactory bulb (OB) allowing dynamic PFC-HC coupling utilizing this input. We used inter-regional coherences and their correlations in rats, breathing at low rate (∼2 Hz) at rest, outside of the short sniffing bouts. We found strong and stable OB-PFC coherence, contrasting OB-HC coherence which was low but highly variable. PFC-HC coupling, however, primarily correlated with the latter, indicating that HC access to the PFC output is dynamically regulated by the responsiveness of HC to the common rhythmic drive. This pattern was present in both theta and non-theta states of waking, whereas PFC-HC communication appeared protected from RR synchronization in sleep states. The findings help to understand the mechanism of rhythmic modulation of non-olfactory cognitive processes by the on-going regular respiration, reported in rodents as well as humans. These mechanisms may be impaired when nasal breathing is limited or in OB-pathology, including malfunctions of the OB epithelium due to infections, such as in COVID-19.