Potential contribution of respiratory rhythm to oscillatory coupling between prefrontal cortex and hippocampus

Breathing in rodents normally appears in a wide range of frequencies, overlapping with delta and theta oscillations involved in state‐ and task‐dependent oscillatory coupling between prefrontal cortex (PFC) and hippocampus (HC). Recent studies reported that the respiratory rhythm (RR), mediated by the olfactory bulb (OB) through monitoring nasal air movement, may promote synchronous oscillations globally in the brain including higher‐order brain networks, such PFC and HC. It remains important to clarify, however, what these networks use respiratory synchrony for — as well as when, how, and why. Aim This study attempts to trace the RR signal to PFC and HC using inter‐regional coherences and their correlations between different neural networks. We focused in particular on the role of OB in RR synchrony and on the resulting RR contribution to communication between PFC and HC. Methods Local field potentials (LFP) were recorded in OB, PFC, and HC along with neck muscle EMG and RR was monitored by recording the diaphragmal EMG (Dia) in undisturbed freely behaving rats (n=8) as well as under urethane anesthesia (n=10). Lasting stationary segments were selected based on these signals, whereas short transients, e.g. episodes of sniffing, were excluded. Coherences were calculated between Dia and LFP signal pairs at theta and RR frequencies and were then correlated in different states: active (AW) and quiet waking (QW), slow‐wave (SWS) and REM sleep, in freely moving rats and in theta and non‐theta states under urethane. Results High Dia‐LFP and inter‐regional LFP‐to‐LFP coherences between pairs of OB, PFC, HC at RR frequency were found in wake (both AW and QW) and urethane‐theta states but were not significant in sleep and non‐theta under urethane, indicating that RR oscillations in PFC and HC are state‐dependent. In these states, OB was found mediating strong RR oscillation to PFC, as OB‐PFC coherence (range: 0.56–0.82 in different states) significantly correlated with coherence between Dia and OB (R2=0.43, p=0.01 in AW), i.e. indicating that the more RR reaches OB, the more OB conveys it further to PFC. OB‐HC coherence was considerably weaker (0.24–0.29 in wake states) and highly variable. HC‐PFC coherence spectra showed two peaks; besides the well‐known theta coupling HC and PFC was also synchronized at RR in AW, QW, and urethane‐theta states (coherences=0.45, 0.45, 0.70, respectively). Importantly however, HC‐PFC RR‐coherence only correlated with RR transmission in the OB‐to‐HC pathway (R2=69, 0.83, 0.72, p<0.02 in QW, AW, and urethan‐theta) but not with OB‐PFC coherence (R2=0.33, 0.15, 0.30, p>0.05) indicating that RR synchrony between HC and PFC primarily depends on RR transmission from OB to HC. Conclusion Both theta and RR are prominent oscillations capable of synchronizing HC‐PFC at similar strengths that may depend on behaviors and cognitive tasks. RR oscillations in PFC, primarily conveyed by OB, were state‐dependent, strong in wake states with different levels of theta coupling (AW and QW). RR oscillations were weaker in HC with relatively low coherence between OB and HC which was more variable however, and its changes were highly correlated with changes in HC‐PFC coherence indicating that the latter was mainly due to common input from OB conveying RR from rhythmic nasal airflow. Support or Funding Information NIMH MH100820 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .