Different types of network oscillations occur in different behavioral, cognitive, or vigilance states. The rodent hippocampus expresses prominent oscillations at frequencies between 4 and 12 Hz, which are superimposed by phase-coupled ␥ oscillations (30 -100 Hz). These patterns entrain multineuronal activity over large distances and have been implicated in sensory information processing and memory formation. Here we report a new type of oscillation at near-frequencies (2-4 Hz) in the hippocampus of urethane-anesthetized mice. The rhythm is highly coherent with nasal respiration and with rhythmic field potentials in the olfactory bulb: hence, we called it hippocampal respiration-induced oscillations. Despite the similarity in frequency range, several features distinguish this pattern from locally generated oscillations: hippocampal respiration-induced oscillations have a unique laminar amplitude profile, are resistant to atropine, couple differently to ␥ oscillations, and are abolished when nasal airflow is bypassed by tracheotomy. Hippocampal neurons are entrained by both the respiration-induced rhythm and concurrent oscillations, suggesting a direct interaction between endogenous activity in the hippocampus and nasal respiratory inputs. Our results demonstrate that nasal respiration strongly modulates hippocampal network activity in mice, providing a long-range synchronizing signal between olfactory and hippocampal networks.

Theta oscillations (4-12 Hz) are thought to provide a common temporal reference for the exchange of information among distant brain networks. On the other hand, faster gamma-frequency oscillations (30-160 Hz) nested within theta cycles are believed to underlie local information processing. Whether oscillatory coupling between global and local oscillations, as showcased by theta-gamma coupling, is a general coding mechanism remains unknown. Here, we investigated two different patterns of oscillatory network activity, theta and respiration-induced network rhythms, in four brain regions of freely moving mice: olfactory bulb (OB), prelimbic cortex (PLC), parietal cortex (PAC), and dorsal hippocampus [cornu ammonis 1 (CA1)]. We report differential state- and region-specific coupling between the slow large-scale rhythms and superimposed fast oscillations. During awake immobility, all four regions displayed a respiration-entrained rhythm (RR) with decreasing power from OB to CA1, which coupled exclusively to the 80- to 120-Hz gamma subband (γ). During exploration, when theta activity was prevailing, OB and PLC still showed exclusive coupling of RR with γ and no theta-gamma coupling, whereas PAC and CA1 switched to selective coupling of theta with 40- to 80-Hz (γ) and 120- to 160-Hz (γ) gamma subbands. Our data illustrate a strong, specific interaction between neuronal activity patterns and respiration. Moreover, our results suggest that the coupling between slow and fast oscillations is a general brain mechanism not limited to the theta rhythm.

We have recently described a slow oscillation in the hippocampus of urethane-anesthetized mice, which couples to nasal respiration and is clearly distinct from co-occurring theta oscillations. Here we set out to investigate whether such type of patterned network activity, which we named "hippocampal respiration rhythm" (HRR), also occurs in awake mice. In freely moving mice, instantaneous respiration rate is extremely variable, and respiration is superimposed by bouts of sniffing. To reduce this variability, we clamped the behavior of the animal to either awake immobility or treadmill running by using a head-fixed setup while simultaneously recording respiration and field potentials from the olfactory bulb (OB) and hippocampus. Head-fixed animals often exhibited long periods of steady respiration rate during either immobility or running, which allowed for spectral and coherence analyses with a sufficient frequency resolution to sort apart respiration and theta activities. We could thus demonstrate the existence of HRR in awake animals, namely, a respiration-entrained slow rhythm with highest amplitude at the dentate gyrus. HRR was most prominent during immobility and running with respiration rates slower than theta oscillations. Nevertheless, HRR could also be faster than theta. Discharges of juxtacellularly recorded cells in CA1 and dentate gyrus were modulated by HRR and theta oscillations. Granger directionality analysis revealed that HRR is caused by the OB and that theta oscillations in OB are caused by the hippocampus. Our results suggest that respiration-coupled oscillations aid the exchange of information between olfactory and memory networks.

Slow brain oscillations are usually coherent over long distances and thought to link distributed cell assemblies. In mice, theta (5–10 Hz) stands as one of the most studied slow rhythms. However, mice often breathe at theta frequency, and we recently reported that nasal respiration leads to local field potential (LFP) oscillations that are independent of theta. Namely, we showed respiration-coupled oscillations in the hippocampus, prelimbic cortex, and parietal cortex, suggesting that respiration could impose a global brain rhythm. Here we extend these findings by analyzing LFPs from 15 brain regions recorded simultaneously with respiration during exploration and REM sleep. We find that respiration-coupled oscillations can be detected in parallel with theta in several neocortical regions, from prefrontal to visual areas, and also in subcortical structures such as the thalamus, amygdala and ventral hippocampus. They might have escaped attention in previous studies due to the absence of respiration monitoring, the similarity with theta oscillations, and the highly variable peak frequency. We hypothesize that respiration-coupled oscillations constitute a global brain rhythm suited to entrain distributed networks into a common regime. However, whether their widespread presence reflects local network activity or is due to volume conduction remains to be determined.

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