Stable frequency response to varying stimulus intensity in a model of the rat olfactory bulb

In the rat olfactory bulb (OB), fast oscillations of the local field potential (LFP) are observed during the respiratory cycle. Gamma-range oscillations (60Hz) occurat the end of inspiration, followed by beta-range oscillations (15-20Hz) during exhalation. These oscillations are highly stereotyped, and their frequencies are stable under various conditions. Here we investigate the effect of stimulus intensity on activity in the OB. Using a double canulation protocol, we show that, although the frequency of the LFP oscillation does depend on the respiratory cycle, it is relatively independent from the intensity of odorant stimulation. In contrast, we found that the individual firing rate of mitral OB cells changes greatly with the intensity of the stimulation. Using a computer model of the OB, where fast oscillations are generated by the interplay between excitatory mitral/tufted cells, and inhibitory granule cells, we found that the difference between individual and population responses can be explained by the role of sub-threshold oscillations in the MCs. Sub-threshold oscillations of the MCs stabilize the frequency of the population oscillation, and allow their firing rate to vary without affecting the population frequency

Stabilisation of beta and gamma oscillation frequency in the mammalian olfactory bulb

International audienceThe dynamics of the mammalian olfactory bulb (OB) is characterized by local field potential (LFP) oscillations either slow, in the theta range (2-10Hz, tightly linked to the respiratory rhythm), or fast, in the beta (15-30Hz) or gamma (40-90Hz) range. These fast oscillations are known to be modulated by odorant features and animal experience or state, but both their mechanisms and implication in coding are still not well understood. In this study, we used a double canulation protocol to impose artificial breathing rhythms to anesthetized rats while recording the LFP in the OB. We observed that despite the changes in the input air flow parameters (frequency or flow rate), the main characteristics of fast oscillations (duration, frequency or amplitude) were merely constant. We thus made the hypothesis that fast beta and gamma oscillations dynamics are entirely determined by the OB network properties and that external stimulation was only able put the network in a state which permits the generation of one or the other oscillations (they are never present simultaneously)

Reshaping of Bulbar Odor Response by Nasal Flow Rate in the Rat

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.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.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

The inextricable relationship betxeen olfaction and rspiration in the rat : study of the impact of sniffing varaitions on bulbar and on odor discrimination

Chez les mamifères terrestres, l’échantillonnage des odeurs (flairage) est inextricablement lié à la respiration. Le flairage contraint à la fois le décours temporel et l’intensité de l’input olfactif. Or le flaireage est un acte dynamique, il peut varier aussi bien en fréquence qu’en débit. Dans une 1ère partie de mon travail de thèse, nous avoins souhaité caractériser l’impact des variations de fréquence et de débit respiratiore sur l’activité du bulbe olfactif. Pour cela, nous avons mis au point une méthode de double trachéotomie chez le rat anesthésié nous permettant de contrôler précisément les flux d’air ans la cavité nasale. En paralèlle, nous avons enregistrer l’acitivité unitaire et de réseau du bulbe olfactif. Nous montrons que les variations de flairage modulent la représentation neuronale bulbaire des odeurs en modifiant à la fois l’activité de décharge des cellules principales et l’occurence des oscillaations du potentiel de champ local. Dans une 2e partie de ma thèse, nous avons souhaitécomprendre quel pouvait être le rôle du flairage chez un animal qui se comporte. Nous avons posé l’hypothèse qu’un animal pouvait adapter sa façon de flaireer en fonction de la qualité des molécules odorantes. Pour tester cette hypothèse, nous avons mis au point un système d’enregeistrement non invasif de la respiration couplé à une tâche de discrimination olfactive chez le rat. Nous montrons non seulement que les animaux peuvent adapter leur flairage en fonction des molécules odorantes masi également en focntion du contexte dans lequel l’odeur est présentée. L’ensemble de ces résultats s’intègre donc dans la problématique plus générale de l’intégration sensori-motrice.In terrestrial mammals, an inextricable link between olfaction and respiration exists due to the periodic sampling of odorant molecules by inhalation. The features of sniffing (or breathing) constrain both the timing and the intensity of the input to the olfactory structures. But rather than being fixed, sniffing in the bahavingrodent is highly dynamic and varies both in frequency and flow rate. During the firs stage of my PhD, I asked to what extent sniffing parameters (frequency and flow rate) variations could affect the olfactory bulb activity. To address this question, I developped a double tracheotomy protocol in anesthetized rats to precisely control and modify the nasal airflow. In parallel, I recorded oldfactory bulbactivities, single-unit activity and local field potentials. We showed that, at the olfactory bulb level, the neutral representation of an odor is highly modified by sampling variations. In fact both the mitral/tufted cell discharge patterns and local field potentials oscilliations were affected by sniffing variations. In the second stage, we wanted to understand the role of sniffing variations in behaving animals. We hypothesized tha t an animal could adapt its sniffing strategy relative to the quality of the odorant molecules. To test this hypothesis, we developped a tool to record sniffing in a non invasive way, and combined it to an olfactory discrimination task in the rat. We showed that animals not only adapted their sniffing relative to the odorant quality but also to the odorant context. Taken together, these results fit into the broader context of sensory-motor integration

L’inextricable relation olfaction-respiration chez le rat : études de l’impact des variations de flairages sur l’activité du bulbe olfactif et sur la discrimination des odeurs

In terrestrial mammals, an inextricable link between olfaction and respiration exists due to the periodic sampling of odorant molecules by inhalation. The features of sniffing (or breathing) constrain both the timing and the intensity of the input to the olfactory structures. But rather than being fixed, sniffing in the bahavingrodent is highly dynamic and varies both in frequency and flow rate. During the firs stage of my PhD, I asked to what extent sniffing parameters (frequency and flow rate) variations could affect the olfactory bulb activity. To address this question, I developped a double tracheotomy protocol in anesthetized rats to precisely control and modify the nasal airflow. In parallel, I recorded oldfactory bulbactivities, single-unit activity and local field potentials. We showed that, at the olfactory bulb level, the neutral representation of an odor is highly modified by sampling variations. In fact both the mitral/tufted cell discharge patterns and local field potentials oscilliations were affected by sniffing variations. In the second stage, we wanted to understand the role of sniffing variations in behaving animals. We hypothesized tha t an animal could adapt its sniffing strategy relative to the quality of the odorant molecules. To test this hypothesis, we developped a tool to record sniffing in a non invasive way, and combined it to an olfactory discrimination task in the rat. We showed that animals not only adapted their sniffing relative to the odorant quality but also to the odorant context. Taken together, these results fit into the broader context of sensory-motor integration.Chez les mamifères terrestres, l’échantillonnage des odeurs (flairage) est inextricablement lié à la respiration. Le flairage contraint à la fois le décours temporel et l’intensité de l’input olfactif. Or le flaireage est un acte dynamique, il peut varier aussi bien en fréquence qu’en débit. Dans une 1ère partie de mon travail de thèse, nous avoins souhaité caractériser l’impact des variations de fréquence et de débit respiratiore sur l’activité du bulbe olfactif. Pour cela, nous avons mis au point une méthode de double trachéotomie chez le rat anesthésié nous permettant de contrôler précisément les flux d’air ans la cavité nasale. En paralèlle, nous avons enregistrer l’acitivité unitaire et de réseau du bulbe olfactif. Nous montrons que les variations de flairage modulent la représentation neuronale bulbaire des odeurs en modifiant à la fois l’activité de décharge des cellules principales et l’occurence des oscillaations du potentiel de champ local. Dans une 2e partie de ma thèse, nous avons souhaitécomprendre quel pouvait être le rôle du flairage chez un animal qui se comporte. Nous avons posé l’hypothèse qu’un animal pouvait adapter sa façon de flaireer en fonction de la qualité des molécules odorantes. Pour tester cette hypothèse, nous avons mis au point un système d’enregeistrement non invasif de la respiration couplé à une tâche de discrimination olfactive chez le rat. Nous montrons non seulement que les animaux peuvent adapter leur flairage en fonction des molécules odorantes masi également en focntion du contexte dans lequel l’odeur est présentée. L’ensemble de ces résultats s’intègre donc dans la problématique plus générale de l’intégration sensori-motrice

Serotonergic regulation of the dopaminergic system: Implications for reward-related functions

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Odorant features differentially modulate beta/gamma oscillatory patterns in anterior versus posterior piriform cortex

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Stability of fast oscillations in the mammalian olfactory bulb: Experiments and modeling

International audienceIn the rat olfactory bulb (OB), fast oscillations of the local field potential (LFP) are observed during the respiratory cycle. Gamma-range oscillations (40-90 Hz) occur at the end of inspiration, followed by beta-range oscillations (15-30 Hz) during exhalation. These oscillations are highly stereotypical, and their frequencies are stable under various conditions. In this study, we investigate the effect of stimulus intensity on activity in the OB. Using a double-cannulation protocol, we showed that although the frequency of the LFP oscillation does depend on the respiratory cycle phase, it is relatively independent of the intensity of odorant stimulation. In contrast, we found that the individual firing rate of mitral OB cells dramatically changed with the intensity of the stimulation. This suggests that OB fast oscillation parameters, particularly frequency, are fully determined by intrinsic OB network parameters. To test this hypothesis, we explored a model of the OB where fast oscillations are generated by the interplay between excitatory mitral/tufted cells and inhibitory granule cells with graded inhibition. We found that our model has two distinct activity regimes depending on the amount of noise. In a low-noise regime, the model displays oscillation in the beta range with a stable frequency across a wide range of excitatory inputs. In a high-noise regime, the model displays oscillatory dynamics with irregular cell discharges and fast oscillations, similar to what is observed during gamma oscillations but without stability of the oscillation frequency with respect to the network external input. Simulations of the full model and theoretical studies of the network's linear response show that the characteristics of the low-noise regime are induced by non-linearities in the model, notably, the saturation of graded inhibition. Finally, we discuss how this model can account for the experimentally observed stability of the oscillatory regimes

Control of gamma vs beta competition in olfactory bulb by the balance between sensory input and centrifugal feedback control

International audienceGamma (40-80Hz) and beta (15-40Hz) oscillations and their associated neuronal assemblies are key features of neuronal sensory processing. However, the mechanisms involved in either their interaction and/or the switch between these different regimes in most sensory systems remain misunderstood. The mammalian olfactory bulb (OB) expresses both gamma and beta oscillations, which appear to be mutually exclusive, and a slower one related to respiration (2-10Hz). Gamma oscillations have been linked to odorant physical properties (quality, intensity) while beta oscillations are strongly increased by odor experience (for reviews see [1,2]). Importantly, the occurrence pattern of these two fast alternating oscillations is intermingled with the respiratory slow rhythm which provides a window for odor discrimination. Based on in vivo recordings and biophysical modeling of the mammalian olfactory bulb (OB), we explored how OB internal dynamics and the balance between sensory and centrifugal inputs control the occurrence and alternation of OB gamma and beta oscillations over a respiratory cycle

Abnormal Serotonin Levels During Perinatal Development Lead to Behavioral Deficits in Adulthood

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