Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats.

Respiratory rhythm (RR) during sniffing is known to couple with hippocampal theta rhythm. However, outside of the short sniffing bouts, a more stable ~ 2 Hz RR was recently shown to rhythmically modulate non-olfactory cognitive processes, as well. The underlying RR coupling with wide-spread forebrain activity was confirmed using advanced techniques, 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) that may support dynamic, flexible PFC-HC coupling utilizing this input. We used inter-regional coherences and their correlations in rats, breathing at low rate (~ 2 Hz), outside of the short sniffing bouts. We found strong and stable OB-PFC coherence in wake states, contrasting OB-HC coherence which was low but highly variable. Importantly, this variability was essential for establishing PFC-HC synchrony at RR, whereas variations of RRO in OB and PFC had no significant effect. 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 olfactory epithelium due to infections, such as in Covid-19.