Respiratory rhythm modulates membrane potential and spiking of nonolfactory neurons.

In recent years, several studies have shown a respiratory drive of the local field potential (LFP) in numerous brain areas so that the respiratory rhythm could be considered as a master clock promoting communication between distant brain locations. However, outside of the olfactory system, it remains unknown whether the respiratory rhythm could shape membrane potential (MP) oscillations. To fill this gap, we co-recorded MP and LFP activities in different nonolfactory brain areas, medial prefrontal cortex (mPFC), primary somatosensory cortex (S1), primary visual cortex (V1), and hippocampus (HPC), in urethane-anesthetized rats. Using respiratory cycle-by-cycle analysis, we observed that respiration could modulate both MP and spiking discharges in all recorded areas during episodes that we called respiration-related oscillations (RRo). Further quantifications revealed that RRo episodes were transient in most neurons (5 consecutive respiratory cycles in average). RRo development in MP was largely correlated with the presence of respiratory modulation in the LFP. By showing that the respiratory rhythm influenced brain activities deep to the MP of nonolfactory neurons, our data support the idea that respiratory rhythm could mediate long-range communication between brain areas.NEW & NOTEWORTHY In this study, we evidenced strong respiratory-driven oscillations of neuronal membrane potential and spiking discharge in various nonolfactory areas of the mammal brain. These oscillations were found in the medial prefrontal cortex, primary somatosensory cortex, primary visual cortex, and hippocampus. These findings support the idea that respiratory rhythm could be used as a common clock to set the dynamics of large-scale neuronal networks on the same slow rhythm.

Respiratory influence on brain dynamics: the preponderant role of the nasal pathway and deep slow regime.

As a possible body signal influencing brain dynamics, respiration is fundamental for perception, cognition, and emotion. The olfactory system has recently acquired its credentials by proving to be crucial in the transmission of respiratory influence on the brain via the sensitivity to nasal airflow of its receptor cells. Here, we present recent findings evidencing respiration-related activities in the brain. Then, we review the data explaining the fact that breathing is (i) nasal and (ii) being slow and deep is crucial in its ability to stimulate the olfactory system and consequently influence the brain. In conclusion, we propose a possible scenario explaining how this optimal respiratory regime can promote changes in brain dynamics of an olfacto-limbic-respiratory circuit, providing a possibility to induce calm and relaxation by coordinating breathing regime and brain state.

The deep and slow breathing characterizing rest favors brain respiratory-drive.

A respiration-locked activity in the olfactory brain, mainly originating in the mechano-sensitivity of olfactory sensory neurons to air pressure, propagates from the olfactory bulb to the rest of the brain. Interestingly, changes in nasal airflow rate result in reorganization of olfactory bulb response. By leveraging spontaneous variations of respiratory dynamics during natural conditions, we investigated whether respiratory drive also varies with nasal airflow movements. We analyzed local field potential activity relative to respiratory signal in various brain regions during waking and sleep states. We found that respiration regime was state-specific, and that quiet waking was the only vigilance state during which all the recorded structures can be respiration-driven whatever the respiratory frequency. Using CO2-enriched air to alter respiratory regime associated to each state and a respiratory cycle based analysis, we evidenced that the large and strong brain drive observed during quiet waking was related to an optimal trade-off between depth and duration of inspiration in the respiratory pattern, characterizing this specific state. These results show for the first time that changes in respiration regime affect cortical dynamics and that the respiratory regime associated with rest is optimal for respiration to drive the brain.

In vivo beta and gamma subthreshold oscillations in rat mitral cells: origin and gating by respiratory dynamics.

In mammals, olfactory bulb (OB) dynamics are paced by slow and fast oscillatory rhythms at multiple levels: local field potential, spike discharge, and/or membrane potential oscillations. Interactions between these levels have been well studied for the slow rhythm linked to animal respiration. However, less is known regarding rhythms in the fast beta (10-35 Hz) and gamma (35-100 Hz) frequency ranges, particularly at the membrane potential level. Using a combination of intracellular and extracellular recordings in the OB of freely breathing rats, we show that beta and gamma subthreshold oscillations (STOs) coexist intracellularly and are related to extracellular local field potential (LFP) oscillations in the same frequency range. However, they are differentially affected by changes in cell excitability and by odor stimulation. This leads us to suggest that beta and gamma STOs may rely on distinct mechanisms: gamma STOs would mainly depend on mitral cell intrinsic resonance, while beta STOs could be mainly driven by synaptic activity. In a second study, we find that STO occurrence and timing are constrained by the influence of the slow respiratory rhythm on mitral and tufted cells. First, respiratory-driven excitation seems to favor gamma STOs, while respiratory-driven inhibition favors beta STOs. Second, the respiratory rhythm is needed at the subthreshold level to lock gamma and beta STOs in similar phases as their LFP counterparts and to favor the correlation between STO frequency and spike discharge. Overall, this study helps us to understand how the interaction between slow and fast rhythms at all levels of OB dynamics shapes its functional output. NEW & NOTEWORTHY In the mammalian olfactory bulb of a freely breathing anesthetized rat, we show that both beta and gamma membrane potential fast oscillation ranges exist in the same mitral and tufted (M/T) cell. Importantly, our results suggest they have different origins and that their interaction with the slow subthreshold oscillation (respiratory rhythm) is a key mechanism to organize their dynamics, favoring their functional implication in olfactory bulb information processing.

The relationship between respiration-related membrane potential slow oscillations and discharge patterns in mitral/tufted cells: what are the rules?

BACKGROUND: A slow respiration-related rhythm strongly shapes the activity of the olfactory bulb. This rhythm appears as a slow oscillation that is detectable in the membrane potential, the respiration-related spike discharge of the mitral/tufted cells and the bulbar local field potential. Here, we investigated the rules that govern the manifestation of membrane potential slow oscillations (MPSOs) and respiration-related discharge activities under various afferent input conditions and cellular excitability states. METHODOLOGY AND PRINCIPAL FINDINGS: We recorded the intracellular membrane potential signals in the mitral/tufted cells of freely breathing anesthetized rats. We first demonstrated the existence of multiple types of MPSOs, which were influenced by odor stimulation and discharge activity patterns. Complementary studies using changes in the intracellular excitability state and a computational model of the mitral cell demonstrated that slow oscillations in the mitral/tufted cell membrane potential were also modulated by the intracellular excitability state, whereas the respiration-related spike activity primarily reflected the afferent input. Based on our data regarding MPSOs and spike patterns, we found that cells exhibiting an unsynchronized discharge pattern never exhibited an MPSO. In contrast, cells with a respiration-synchronized discharge pattern always exhibited an MPSO. In addition, we demonstrated that the association between spike patterns and MPSO types appeared complex. CONCLUSION: We propose that both the intracellular excitability state and input strength underlie specific MPSOs, which, in turn, constrain the types of spike patterns exhibited.

Reshaping of bulbar odor response by nasal flow rate in the rat.

BACKGROUND: The impact of respiratory dynamics on odor response has been poorly studied at the olfactory bulb level. However, it has been shown that sniffing in the behaving rodent is highly dynamic and varies both in frequency and flow rate. Bulbar odor response could vary with these sniffing parameter variations. Consequently, it is necessary to understand how nasal airflow can modify and shape odor response at the olfactory bulb level. METHODOLOGY AND PRINCIPAL FINDINGS: To assess this question, we used a double cannulation and simulated nasal airflow protocol on anesthetized rats to uncouple nasal airflow from animal respiration. Both mitral/tufted cell extracellular unit activity and local field potentials (LFPs) were recorded. We found that airflow changes in the normal range were sufficient to substantially reorganize the response of the olfactory bulb. In particular, cellular odor-evoked activities, LFP oscillations and spike phase-locking to LFPs were strongly modified by nasal flow rate. CONCLUSION: Our results indicate the importance of reconsidering the notion of odor coding as odor response at the bulbar level is ceaselessly modified by respiratory dynamics.

Respiration-gated formation of gamma and beta neural assemblies in the mammalian olfactory bulb.

A growing body of data suggests that information coding can be achieved not only by varying neuronal firing rate, but also by varying spike timing relative to network oscillations. In the olfactory bulb (OB) of a freely breathing anaesthetized mammal, odorant stimulation induces prominent oscillatory local field potential (LFP) activity in the beta (10-35 Hz) and gamma (40-80 Hz) ranges, which alternate during a respiratory cycle. At the same time, mitral/tufted (M/T) cells display respiration-modulated spiking patterns. Using simultaneous recordings of M/T unitary activities and LFP activity, we conducted an analysis of the temporal relationships between M/T cell spiking activity and both OB beta and gamma oscillations. We observed that M/T cells display a respiratory pattern that pre-tunes instantaneous frequencies to a gamma or beta regime. Consequently, M/T cell spikes become phase-locked to either gamma or beta LFP oscillations according to their frequency range and respiratory pattern. Our results suggest that slow respiratory dynamics pre-tune M/T cells to a preferential fast rhythm (beta or gamma) such that a spike-LFP coupling might occur when units and oscillation frequencies are in a compatible range. This double-coupling process might define two complementary beta- and gamma-neuronal assemblies along the course of a respiratory cycle.

Odor vapor pressure and quality modulate local field potential oscillatory patterns in the olfactory bulb of the anesthetized rat.

A central question in chemical senses is the way that odorant molecules are represented in the brain. To date, many studies, when taken together, suggest that structural features of the molecules are represented through a spatio-temporal pattern of activation in the olfactory bulb (OB), in both glomerular and mitral cell layers. Mitral/tufted cells interact with a large population of inhibitory interneurons resulting in a temporal patterning of bulbar local field potential (LFP) activity. We investigated the possibility that molecular features could determine the temporal pattern of LFP oscillatory activity in the OB. For this purpose, we recorded the LFPs in the OB of urethane-anesthetized, freely breathing rats in response to series of aliphatic odorants varying subtly in carbon-chain length or functional group. In concordance with our previous reports, we found that odors evoked oscillatory activity in the LFP signal in both the beta and gamma frequency bands. Analysis of LFP oscillations revealed that, although molecular features have almost no influence on the intrinsic characteristics of LFP oscillations, they influence the temporal patterning of bulbar oscillations. Alcohol family odors rarely evoke gamma oscillations, whereas ester family odors rather induce oscillatory patterns showing beta/gamma alternation. Moreover, for molecules with the same functional group, the probability of gamma occurrence is correlated to the vapor pressure of the odor. The significance of the relation between odorant features and oscillatory regimes along with their functional relevance are discussed.

Respiratory modulation of olfactory neurons in the rodent brain.

In this review we report data from freely breathing animals in an attempt to show how respiratory dynamics can influence bulbar and cortical activity. Relying on in vivo data as well as in vitro observations, we try to emphasize the multiple mechanisms that underlie this modulation, its multiple origins, and its possible functional role.

Rhythm sequence through the olfactory bulb layers during the time window of a respiratory cycle.

The mammalian olfactory bulb is characterized by prominent oscillatory activity of its local field potentials. Breathing imposes the most important rhythm. Other rhythms have been described in the beta- and gamma-frequency ranges. We recorded unitary activities in different bulbar layers simultaneously with local field potentials in order to examine the different relationships existing between (i) breathing and field potential oscillations, and (ii) breathing and spiking activity of different cell types. We show that, whatever the layer, odour-induced gamma oscillations always occur around the transition point between inhalation and exhalation while beta oscillations appear during early exhalation and may extend up to the end of inhalation. By contrast, unitary activities exhibit different characteristics according to the layer. They vary in (i) their temporal relationship with respect to the respiratory cycle; (ii) their spike rates; (iii) their temporal patterns defined according to the respiratory cycle. The time window of a respiratory cycle might thus be split into three main epochs based on the deceleration of field potential rhythms (from gamma to beta oscillations) and a simultaneous gradient of spike discharge frequencies ranging from 180 to 30 Hz. We discuss the possibility that each rhythm could serve different functions as priming, gating or tuning for the bulbar network.