Nadine Ravel

Learning Modulation of Odor-Induced Oscillatory Responses in the Rat Olfactory Bulb: A Correlate of Odor Recognition?

In the first relay of information processing, the olfactory bulb (OB), odors are known to generate specific spatial patterns of activity. Recently, in freely behaving rats, we demonstrated that learning modulated oscillatory activity in local field potential (LFP), in response to odors, in both β (15-40 Hz) and γ (60-90 Hz) bands. The present study further characterized this odor-induced oscillatory activity with emphasis on its spatiotemporal distribution over the olfactory bulb and on its relationship with improvement of behavioral performances along training. For that purpose, LFPs were simultaneously recorded from four locations in the OB in freely moving rats performing an olfactory discrimination task. Electrodes were chronically implanted near relay neurons in the mitral cell body layer. Time-frequency methods were used to extract signal characteristics (amplitude, frequency, and time course) in the two frequency bands. Before training, odor presentation produced, on each site, a power decrease in γ oscillations and a weak but significant increase in power of β oscillations (∼25 Hz). When the training was achieved, these two phenomena were amplified. Interestingly, the β oscillatory response showed several significant differences between the anterodorsal and posteroventral regions of the OB. In addition, clear-cut β responses occurred in the signal as soon as animals began to master the task. As a whole, our results point to the possible functional importance of β oscillatory activity in the mammalian OB, particularly in the context of olfactory learning.

Olfactory learning modifies the expression of odour-induced oscillatory responses in the gamma (60-90 Hz) and beta (15-40 Hz) bands in the rat olfactory bulb

This study addressed the question of the possible functional relevance of two different oscillatory activities, beta and gamma (15–40 and 60–90 Hz, respectively) for perception and memory processes in olfactory areas of mammals. Local field potentials were recorded near relay olfactory bulb neurons while rats performed an olfactory discrimination task. Signals reflected the mass activity from this region and characteristics of oscillatory activities were used as an index of local synchrony. Beta and gamma oscillatory activities were quantified by time‐frequency methods before during and after odour sampling. In rats early in their training, olfactory sampling was associated with a significant decrease in power in the gamma band in parallel with a weak but significant increase in the beta band (centred on 27 Hz). Several days later, in well‐trained rats, the gamma oscillatory depression was significantly enhanced both in duration and amplitude. It appeared within the 500 ms time period preceding odour onset and was further reduced during the odour period. Concurrently the beta oscillatory response (now centred on 24 Hz) during odour sampling was amplified by a twofold factor. The beta band response was modulated according to the chemical nature of the stimuli and rats behavioural response. This study showed for the first time that odour sampling in behaving animals is associated with a clear shift in the olfactory bulb neuronal activity from a gamma to a beta oscillatory regime. Moreover, the data stress the importance of studying the odour‐induced beta activity and its relation to perception and memory.

Scopolamine injection into the olfactory bulb impairs short-term olfactory memory in rats.

A previous experiment showed that systemic administration of the muscarinic antagonist scopolamine altered delayed matching in an olfactory task in rats. The present experiment tested whether the impairment could result from blockade of the cholinergic transmission in the first relay structure of the olfactory system, the olfactory bulb. Drug was infused directly into both olfactory bulbs before test sessions. Results showed that the intrabulbar infusion reproduced the effect of the systemic administration. With a 4-s delay between target odor and choice test, performances of treated rats remained unchanged; but with a 30-s delay, rats performed randomly. Results from a complementary electrophysiological experiment in anesthetized rats support the idea that scopolamine injected into the olfactory bulb was unlikely to have reached more central structures. Further evidence for the involvement of pure sensory areas in short-term memory is concluded.

Learning-induced oscillatory activities correlated to odour recognition: a network activity

In trained behaving rats, the expression of a prominent beta oscillatory activity in the olfactory system was previously identified as a correlate of odour recognition. The aim of the present study was to assess the putative role of a functional coupling between the olfactory bulb (OB) and higher structures in this activity. We performed a unilateral inactivation of the medial part of the olfactory peduncle by lidocaine infusion. Inactivation deprived the OB from most of its centrifugal afferences, including feedback connections from the piriform cortex (PC) while sparing the ascending fibres from the OB to higher cortical structures. This treatment reduced the amplitude of odour‐induced oscillatory beta responses both in OB and PC. In parallel, gamma activity classically observed in these two structures during spontaneous activity displayed a strong enhancement. Results suggest that odour‐induced oscillatory response could be the emergent feature of an olfactory functional network set up through learning.

Scopolamine impairs delayed matching in an olfactory task in rats

The action of the cerebral cholinergic system seems to be important for remembering events over short time intervals. We decided to test this hypothesis in the rat by developing an original model of short term memory based on the olfactory sensory modality which is a major determinant in the animal behaviour. The principle of the experiment was a “delayed match-to-sample” test performed in a classical T maze divided into two compartments. In the first compartment, rats received an odorant stimulation, then, in the second, they had to discriminate between the two arms odorized differently. To receive a food reinforcement, the animals had to enter the arm signaled by the odor presented in the first part of the maze. The test was performed with (Short-term memory condition) or without (Immediate memory condition) a variable delay between the first odor sampling and the discrimination task. Both tests were performed with control and scopolamine-treated animals (0.5, 0.125 and 0.0625 mg/kg IP). An injection of scopolamine (0.5 mg/kg) impaired performances, even when no retention of the odor was required. However, lower doses (0.125, 0.0625 mg/kg) selectively altered performances in the short term memory condition. These results suggest that intact muscarinic transmission is required for an olfactory cue to be used over a short time after its presentation.

A study of the effects of noradrenaline in the rat olfactory bulb using evoked field potential response.

In the rat, the main olfactory bulb receives a strong noradrenergic (NA) input from the locus coeruleus which is critical for different types of olfactory learning. However, the resulting effect of NA modulation on on the olfactory bulb electrical activity and its pharmacology are not well understood. In this study, we investigated the action of NA on the bulbar neuronal population using evoked field potentials (EFP) elicited antidromically in the olfactory bulb of anesthetized rats, by stimulation of the lateral olfactory tract (LOT). EFPs in response to single and paired-pulse stimulation of the LOT were collected before, during and until 2 h after a 10 min perfusion of pharmacological agents through a push-pull cannula. Four concentrations of NA were tested ranging from 10(-5) M to 10(-2) M. NA induced a reversible dose-dependent effect. The major effect was observed at 10(-3) M. It consisted of an increase in Component 2 amplitude (depolarization of granules cell dendrites) and a decrease in Component 3 amplitude (depolarization of granule cell bodies). In parallel, paired-pulse inhibition of mitral cells by granule cells was increased. The alpha 1 agonist phenylephrine (10(-3) M) mimicked most of the effects of NA whereas the alpha 1 antagonist prazosin (10(-3) M) blocked its main action. Isoproterenol (beta agonist, 10(-3) M) and clonidine (alpha 2 agonist, 10(-3) M) could not reproduce the effects of NA. Thus mainly through the activation of alpha 1 receptors, NA enhances synaptic activation of granule cells and increases feed-back inhibition of mitral cells. Consequences of such effects in the context of learning and memory are discussed.

The Way an Odor Is Experienced during Aversive Conditioning Determines the Extent of the Network Recruited during Retrieval: A Multisite Electrophysiological Study in Rats

Recent findings have revealed the importance of orthonasal and retronasal olfaction in food memory, especially in conditioned odor aversion (COA); however, little is known about the dynamics of the cerebral circuit involved in the recognition of an odor as a toxic food signal and whether the activated network depends on the way (orthonasal vs retronasal) the odor was first experienced. In this study, we mapped the modulations of odor-induced oscillatory activities through COA learning using multisite recordings of local field potentials in behaving rats. During conditioning, orthonasal odor alone or associated with ingested odor was paired with immediate illness. For all animals, COA retrieval was assessed by orthonasal smelling only. Both types of conditioning induced similarly strong COA. Results pointed out (1) a predictive correlation between the emergence of powerful beta (15–40 Hz) activity and the behavioral expression of COA and (2) a differential network distribution of this beta activity according to the way the animals were exposed to the odor during conditioning. Indeed, for both types of conditioning, the aversive behavior was predicted by the emergence of a strong beta oscillatory activity in response to the odor in the olfactory bulb, piriform cortex, orbitofrontal cortex, and basolateral amygdala. This network was selectively extended to the infralimbic and insular cortices when the odor was ingested during acquisition. These differential networks could participate in different food odor memory; these results are discussed in line with recent behavioral results that indicate that COA can be formed over long odor-illness delays only if the odor is ingested.

Learning-induced modulation of oscillatory activities in the mammalian olfactory system: The role of the centrifugal fibres

In the mammalian olfactory system, oscillations related to odour representation have been described in field potential activities. Previous results showed that in olfactory bulb (OB) of awake rats engaged in an olfactory learning, odour presentation produced a decrease of oscillations in gamma frequency range (60-90 Hz) associated with a power increase in beta frequency range (15-40 Hz). This response pattern was strongly amplified in trained animals. The aim of this work was twofold: whether learning also induces similar changes in OB target structures and whether such OB response depends on its centrifugal inputs. Local field potentials (LFPs) were recorded through chronically implanted electrodes in the OB, piriform and enthorhinal cortices of freely moving rats performing an olfactory discrimination. Oscillatory activities characteristics (amplitude, frequency and time-course) were extracted in beta and gamma range by a wavelet analysis. First, we found that odour induced beta oscillatory activity was present not only in the OB, but also in the other olfactory structures. In each recording site, characteristics of the beta oscillatory responses were dependent of odour, structure and learning level. Unilateral section of the olfactory peduncle was made before training, and LFPs were symmetrically recorded in the two bulbs all along the acquisition of the learning task. Data showed that deprivation of centrifugal feedback led to an increase of spontaneous gamma activity. Moreover, under this condition olfactory learning was no longer associated with the typical large beta band. As a whole, learning modulation of the beta oscillatory response in olfactory structures may reflect activity of a distributed functional network involved in odour representation.

Functional coupling in rat central olfactory pathways: a coherence analysis

This experiment determined the importance of functional coupling between structures of central olfactory pathways: the olfactory bulb (OB), anterior (APC), posterior (PPC) parts of the piriform cortex and lateral entorhinal cortex (EC). From local field potential signals obtained in awake rats, coupling during spontaneous activity was estimated with variables reflecting level of coherence computed with a dynamical method. Results revealed a clear hierarchy in the strength of coupling between structures with dissociation within the piriform cortex: PPC was more tightly coupled with the EC than with APC. Systemic injection of a cholinergic antagonist, scopolamine, suggested that tonic coupling is strongly mediated by cortico-cortical connections and not by an external synchronizer, except between OB and APC.

Modular structure of functional networks in olfactory memory.

Graph theory enables the study of systems by describing those systems as a set of nodes and edges. Graph theory has been widely applied to characterize the overall structure of data sets in the social, technological, and biological sciences, including neuroscience. Modular structure decomposition enables the definition of sub-networks whose components are gathered in the same module and work together closely, while working weakly with components from other modules. This processing is of interest for studying memory, a cognitive process that is widely distributed. We propose a new method to identify modular structure in task-related functional magnetic resonance imaging (fMRI) networks. The modular structure was obtained directly from correlation coefficients and thus retained information about both signs and weights. The method was applied to functional data acquired during a yes-no odor recognition memory task performed by young and elderly adults. Four response categories were explored: correct (Hit) and incorrect (False alarm, FA) recognition and correct and incorrect rejection. We extracted time series data for 36 areas as a function of response categories and age groups and calculated condition-based weighted correlation matrices. Overall, condition-based modular partitions were more homogeneous in young than elderly subjects. Using partition similarity-based statistics and a posteriori statistical analyses, we demonstrated that several areas, including the hippocampus, caudate nucleus, and anterior cingulate gyrus, belonged to the same module more frequently during Hit than during all other conditions. Modularity values were negatively correlated with memory scores in the Hit condition and positively correlated with bias scores (liberal/conservative attitude) in the Hit and FA conditions. We further demonstrated that the proportion of positive and negative links between areas of different modules (i.e., the proportion of correlated and anti-correlated areas) accounted for most of the observed differences in signed modularity. Taken together, our results provided some evidence that the neural networks involved in odor recognition memory are organized into modules and that these modular partitions are linked to behavioral performance and individual strategies.