Respiratory coupling between prefrontal cortex and hippocampus of rats anaesthetized with urethane in theta and non-theta states

Abstract

Respiratory modulation of forebrain activity, long considered hard to reliably separate from breathing artefacts, has been firmly established in recent years using a variety of advanced techniques. Respiratory-related oscillation (RRO) is derived from rhythmic nasal airflow in the olfactory bulb (OB) and is conveyed to higher order brain networks, including the prefrontal cortex (PFC) and hippocampus (HC), where it may potentially contribute to communication between these structures by synchronizing their activities at the respiratory rate. RRO was shown to change with sleep-wake states; it is strongest in quiet waking, somewhat less in active waking, characterized with theta activity in the HC, and absent in sleep. The goal of this study was to test RRO synchronization between PFC and HC under urethane anaesthesia where theta and non-theta states spontaneously alternate. We found that in theta states, PFC-HC coherences significantly correlated with OB-HC but not with OB-PFC, even though RRO was stronger in PFC than in HC. In non-theta states, PFC-HC synchrony correlated with coherences connecting OB to either PFC or HC. Thus, similar to freely behaving rats, PFC-HC synchrony at RRO was primarily dependent on the response of HC to the common rhythmic drive, but only in theta state. The findings help outlining the value and the limits of applications in which urethane-anaesthetized rats can be used for modelling the neural mechanisms of RRO in behaving animals.

Keywords: coupling of distant networks; dynamic coupling; oscillatory synchrony; respiratory-related oscillations.

FIGURE 1

Sample recording of diaphragmal electromyogram (EMG) along with local field potentials (LFPs) in olfactory bulb (OB), prefrontal cortex (PFC) and hippocampus (HC). (a) Time-frequency (0–7.5 Hz) plot showing alternation of theta–non-theta–theta states. (b) Traces of original recordings in a theta state. Respiratory rhythm (black) was derived from diaphragmal EMG (grey)

FIGURE 2

Comparison of state-dependent respiratory related oscillation (RRO) coherences in prefrontal cortex (PFC) and hippocampus (HC) transferred through olfactory bulb (OB) in urethane-anaesthetized rats. (a) Diaphragmal (dia) power and dia-OB coherence during theta and non-theta states. Dia-power, dia-OB coherence spectra are shown in individual experiments (grey) and averaged over the group (dark). (b) Coherence between OB and higher order networks of PFC and HC. Average coherence spectra over RRO and theta frequencies (1–10 Hz; left) and peak coherence at RRO frequency (right; squares: group averages, dots: individual experiments; individual rats are marked using the same colour in the two states). Note strong state dependence with nearly identical dia-OB and OB-PFC coherences in both states and considerably lower OB-HC coherence. (c) Variability of coherence values in individual experiments. Note high coefficient of variation of OB-HC in theta state, twice exceeding dia-OB and OB-PFC

FIGURE 3

The relationship between peak respiratory related oscillation (RRO) coherences connecting dia to olfactory bulb (OB) and those connecting OB to prefrontal cortex (PFC) (a) and hippocampus (HC) networks (b). Note significant (p < .01) positive correlation of dia-OB with OB-PFC (R² = .87 in theta and R² = .80 in non-theta state) and OB-HC (R² = .99 in theta and R² = .78 in non-theta state)

FIGURE 4

(a) Prefrontal cortex-hippocampus (PFC-HC) coherences under urethane anaesthesia at respiratory related oscillation (RRO) in non-theta and theta states and at theta frequency in theta states. Squares: group averages, dots: individual experiments (individual rats marked by the same colours as in Figure 2) (b and c) Correlation between peak RRO coherences connecting PFC and HC versus those between olfactory bulb (OB) and dia, PFC, HC signals in theta and non-theta states. All correlations with PFC-HC were significant (<.04 in theta and p < .001) in non-theta state), except OB-PFC in theta state (R² = .30, p = .16)