Dissertations / Theses on the topic 'Olfaction'

Recent evidence has contributed to change the view according to which action representation chiefly depends on visual information. In particular, research on hand grasping actions has emphasized that a multimodal interplay across vision, audition, the sense of touch, and proprioception occurs when performing and understanding an action (e.g., Castiello, 1996; Patchay, Castiello, & Haggard, 2003; Gazzola, Aziz-Zadeh, & Keysers, 2006; Zahariev & MacKenzie, 2007). The experimental work included in the present thesis aimed at extending the multisensory aspects of action representation to the olfactory domain. I first addressed this issue from the perspective of action execution by asking participants to reach and grasp a target-object under different circumstances of visual and olfactory stimulation. The angular excursion at the level of individual digits, digits’ angular distance, and arm movement duration were recorded. Next, I focused on action understanding by asking participants to observe others’ grasping actions under different visual and olfactory conditions. Here, cerebral activity of the neural system responsible for action understanding, i.e., the Action Observation System (AOS) was recorded. An overview of this experimentation is outlined in the following section. OVERVIEW OF THE PRESENT RESEARCH In the first two experiments (Thesis Chapters 3 and 4) participants were requested to reach towards and grasp either a small or a large visual target calling for different types of grasp, precision grip (PG) and whole hand grasp (WHG), respectively. This task was performed in the absence or in the presence of an odour associated with objects that, if grasped, would require a PG or a WHG. The aim of these experiments was twofold. First, to understand whether the central nervous system (CNS) can use olfactory information to select and execute a ‘grasp’ motor plan. Second, to shed light on how detailed the motor commands embedded within the ‘grasp’ plans elicited by an object’s olfactory representation are. The results showed that merely smelling the odour associated with a small and a large object activates the kinematic parameterization of the action appropriate for grasp that object, i.e., PG and WHG, respectively. Therefore, the CNS is able to convert the geometric features of an olfactory-encoded object (e.g., size) into the motor prototype for interacting with that object. In other words, the visuomotor mechanism underlying the control of action (e.g., Castiello, 1996) appears to be sensitive to olfactory information. From a perceptual perspective, the representation evoked by the odour seems to contain highly detailed information regarding the object (i.e., volumetric features). This is because the effect of odour ‘size’ was played out on the hand posture at the level of individual digits’ motion. If olfaction had provided a blurred and holistic object’s representation (i.e., a low spatial-resolution of the object’s image), then the odour would have not affected would have not affected the hand in its entirety. From a motor perspective, the olfactory representation seems to be mapped into the action vocabulary with a certain degree of reliability. The elicited motor plan is not an incomplete primal sketch which only provides a preliminary descriptive in the terms of motor execution but it embodies specific and selective commands for handling the ‘smelled’ object. In the experiments described above the odour associated with the object was always delivered before movement initiation and before the target became visually available. For the motor control system this entailed to prioritize the ‘olfactory’ non-target object with respect to the visual target. Specifically, planning and execution of action was first based on the sense of smell. In this respect, previous research on grasping actions revealed that visual nontarget-objects do not activate the corresponding ‘grasp’ plans when prior knowledge regarding the visual target is given to participants (e.g., Castiello, 1996). In order to investigate whether this caveat also applies for nontarget-objects signalled via olfaction, I performed an experiment (Thesis Chapters 5) similar to those reported above, but participants were given sufficient time to code for the visual target before movement initiation. The results showed that in such circumstances the odour ‘size’ did modulate the temporal organization of the arm movement. Therefore, even when olfactory information plays a secondary role with respect to visual information for action guidance, the olfactory-encoded object is represented within the motor system. And, traces of the ‘grasp’ motor plan associated with the olfactory object remain evident at the level of the arm movement. Having demonstrated the influence that olfactory stimuli might have for the control of action I reasoned that such phenomenon might be relevant for investigating possible gender differences in the use of olfactory information within the action domain (e.g., Ecuyer-Dab & Robert, 2004). Therefore by using an experimental paradigm similar to that reported in Thesis Chapter 4, I investigated whether gender differences were evident when odours of objects had to be mapped into the corresponding ‘grasp’ motor plans (Thesis Chapter 6). The results showed that for men arm-movement duration increased when the ‘size’ of the odour did not match the size of the visual target. Whereas, for women such effect was not revealed. Remember that a lengthening in movement duration was taken as evidence for an odour-induced activation of the ‘grasp’ motor plans associated with the ‘smelled-objects’ (Thesis Chapter 4). Therefore, it appears that male sense of smell is action-oriented, i.e., tailored to elicit specific and selective motor commands for act upon olfactory-encoded objects. Whereas, in line with previous evidences stemming from research on human olfaction, the female sense of smell would be perception-oriented, i.e., optimised to detect, discriminate, identify, recognise, and categorise odours (e.g., Brand & Millot, 2001). Once documented that the sense of smell provides useful information for planning and execute an action I investigated whether olfactory cues may also contribute to the understanding of others’ actions. The fMRI experiment reported in Thesis Chapter 7 was conceived to specifically address this issue. The results showed that the neural system devoted to action understanding (i.e., the ASO) represented both a hand grasping an ‘olfactory’ object and a mimed hand grasp. Importantly, evidence that the AOS was also able to differentiate between these two type of actions was also found. The discrimination process might solely be ascribed to the olfactory information which signalled the target-object. Therefore, the role played by olfactory information in action understanding was demonstrated. With this in mind the central advance of the present work is twofold. First, I demonstrated that processes of selection for the control of actions may be based on olfactory information. This was done by linking current advances in the methodology for recording hand kinematics and paradigms considering the presence of nontarget-object. Second, I provided evidence for the contribution of olfactory information to the understanding of other’s actions. This was achieved by combining the fMRI technique with an action observation paradigm. REFERENCES Brand, G., & Millot, J. L. (2001). Sex differences in human olfaction: between evidence and enigma. Quarterly Journal of Experimental Psychology, 54, 259-270. Castiello, U. (1996). Grasping a fruit: selection for action. Journal of Experimental Psychology: Human Perception and Performance, 22, 582-603. Ecuyer-Dab, I., & Robert, M. (2004). Have sex differences in spatial ability evolved from male competition for mating and female concern for survival? Cognition, 91, 221-257. Gazzola, V., Aziz-Zadeh, L., & Keysers, C. (2006). Empathy and the somatotopic auditory mirror system in humans. Current Biology, 16, 1824-1829. Patchay, S., Castiello, U., & Haggard, P. (2003). A crossmodal interference effect in grasping objects. Psychological Bulletin Reviews, 10, 924-931. Zahariev M. A., & MacKenzie, C. L. (2007) Grasping at thin air: multimodal contact cues for reaching and grasping. Experimental Brain Research, 180, 69-84.
Evidenze ottenute da studi recenti hanno cambiato la concezione secondo cui la rappresentazione dell’azione si basa principalmente sulle informazioni di natura visiva. In particolare, la ricerca sulle azioni di prensione ha dimostrato che si verifica un’interazione tra la visione, l’udito, il tatto e la propriocezione sia quando una persona esegue un’azione sia quando cerca di capire l’azione di un altro individuo (Castiello, 1996; Patchay, Castiello, & Haggard, 2003; Gazzola, Aziz-Zadeh, & Keysers, 2006; Zahariev & MacKenzie, 2007). Il lavoro sperimentale riportato nella presente tesi ha lo scopo di estendere gli aspetti multisensoriali della rappresentazione dell’azione al dominio olfattivo. Per prima cosa ho trattato questa questione dalla prospettiva dell’esecuzione dell’azione chiedendo ai partecipanti di raggiungere ed afferrare un oggetto target in diverse condizioni di stimolazione visiva ed olfattiva. Ho registrato l’escursione angolare a livello delle singole giunture delle dita della mano e delle distanze tra le dita. Inoltre ho misurato la durata del movimento del braccio. Poi mi sono concentrato sulla comprensione dell’azione chiedendo ai partecipanti di osservare le azioni di prensione compiute da altri individui in diverse condizioni di stimolazione visiva ed olfattiva. Qui, usando la risonanza magnetica funzionale (fMRI), ho registrato l’attività cerebrale dell’Action Observation System (AOS), la rete di aree responsabile della comprensione dell’azione. Nella seguente sezione fornisco un riassunto di questa sperimentazione. RIASSUNTO DELLA RICERCA Nei primi due esperimenti (Capitoli 3 e 4 della Tesi) i partecipanti raggiungevano ed afferravano degli oggetti target grandi oppure piccoli che richiedevano rispettivamente un precision grip (PG) e un whole hand grasp (WHG). Questo compito era svolto in assenza o in presenza di un odore associato con un oggetto che, se afferrato, avrebbe richiesto un PG o un WHG. L’obiettivo di questi esperimenti era duplice. Innanzitutto volevo capire se il sistema nervoso centrale (SNC) può usare l’informazione olfattiva per selezionare ed eseguire un piano motorio di prensione. Poi volevo valutare quanto sono dettagliati i comandi motori inclusi nel piano di prensione eventualmente attivato dall’odore. I risultati mostrano che semplicemente annusare l’odore associato con un oggetto grande oppure piccolo attiva la parametrizzazione cinematica dell’azione di prensione appropriata per agire su quell’oggetto, i.e., rispettivamente un PG e un WHG. Quindi, il SNC è in grado di convertire le caratteristiche geometriche di un oggetto codificato attraverso l’olfatto nel piano motorio per interagire con quell’oggetto. In altre parole il meccanismo visuomotorio sottostante il controllo dell’azione (Castiello, 1996) è sensibile all’informazione olfattiva. Da una prospettiva percettiva, la rappresentazione evocata dall’odore contiene informazioni altamente dettagliate circa l’oggetto (i.e., caratteristiche volumetriche). Questo perché l’effetto di ‘dimensione’ dell’odore è evidente a livello del movimento delle singole giunture delle singole dita della mano. Se l’olfatto avesse fornito una rappresentazione olistica e non dettagliata dell’oggetto (i.e., un’immagine dell’oggetto a bassa risoluzione spaziale), l’odore non avrebbe modulato la mano nella sua interezza. Da una prospettiva motoria, la rappresentazione olfattiva è mappata nel vocabolario delle azioni con un buon grado di affidabilità. Il piano motorio attivato dall’odore non è una bozza incompleta e primitiva che fornisce solo una descrizione preliminare in termini di esecuzione motoria ma incorpora comandi specifici e selettivi per manipolare l’oggetto ‘annusato’. Negli esperimenti appena descritti l’odore associato con l’oggetto era sempre somministrato prima dell’inizio del movimento e prima che l’oggetto target diventasse visibile. Per il sistema di controllo motorio questo implica una priorità dell’oggetto ‘olfattivo’ nontareget rispetto al target visivo. Nello specifico, la pianificazione e l’esecuzione dell’azione è basata sull’informazione olfattiva. A tal proposito, la ricerca sulle azioni di prensione ha mostrato che gli oggetti visivi nontarget non attivano i corrispondenti piani motori di prensione quando i partecipanti conoscono in anticipo il target (Castiello, 1996). Al fine di investigare se ciò vale anche per gli oggetti ‘olfattivi’ nontarget, ho condotto un esperimento simile a quelli riportati sopra, tuttavia, qui i partecipanti avevano tempo di codificare il target visivo prima dell’inizio del movimento (Capitolo 5 della Tesi). I risultati mostrano che la ‘dimensione’ dell’odore modula l’organizzazione temporale del movimento del braccio. Quindi, anche quando l’informazione olfattiva gioca un ruolo secondario rispetto all’informazione visiva per la guida dell’azione, l’oggetto ‘olfattivo’ è rappresentato nel sistema motorio. Dopo aver dimostrato l’influenza degli stimoli olfattivi sul controllo dell’azione, ho pensato che tale fenomeno poteva essere rilevante per investigare possibili differenze di genere nell’uso dell’informazione olfattiva entro il dominio dell’azione (Ecuyer-Dab & Robert, 2004). Quindi, usando un paradigma sperimentale simile a quello riportato nel Capitolo 4 della Tesi, ho valutato se la capacità di trasformare gli odori degli oggetti nei corrispondenti piani motori varia a seconda del genere (Capitolo 6 della Tesi). I risultati mostrano che per i maschi la durata del movimento del braccio aumenta quando la ‘dimensione’ dell’odore non corrisponde alla dimensione del target visivo. D’altra parte, per le femmine questo effetto non è evidente. Si ricordi che l’aumento della durata del movimento del braccio indica l’attivazione del piano motorio di prensione associato con l’oggetto ‘annusato’ (Capitolo 4 della Tesi). Quindi, sembra che l’olfatto dei maschi sia orientato all’azione, i.e., predisposto ad innescare comandi motori specifici e selettivi per agire sugli oggetti codificati a livello olfattivo. Invece, in linea con precedenti evidenze (Brand & Millot, 2001), l’olfatto femminile sarebbe orientato alla percezione, i.e., ottimizzato per rilevare, discriminare, identificare, riconoscere e categorizzare odori. Una volta dimostrato che l’olfatto fornisce informazioni utili per la pianificazione e l’esecuzione dell’azione, ho indagato se gli indizi olfattivi possono contribuire anche alla comprensione dell’azione altrui. L’esperimento fMRI riportato nel Capitolo 7 della Tesi è stato disegnato per trattare questa questione. I risultati mostrano che l’AOS rappresenta sia una mano che afferra un oggetto di cui si sente l’odore che una prensione mimata. Inoltre l’AOS è in grado di differenziare tra questi due tipi di azione. Questo processo di discriminazione è imputabile solamente all’informazione olfattiva che segnala l’oggetto afferrato da un altro individuo. Quindi il ruolo giocato dall’informazione olfattiva nella comprensione dell’azione risulta dimostrato. In conclusione le evidenze riportate nella mia tesi forniscono due contributi fondamentali all’idea di rappresentazione dell’azione multimodale. Primo, il processo di selezione dei piani motori per il controllo delle azioni può basarsi sull’informazione olfattiva. Questa nozione poggia sui dati ottenuti combinando le recenti tecniche di registrazione delle cinematiche della mano con i paradigmi che considerano la presenza di oggetti nontarget. Secondo, l’olfatto contribuisce alla comprensione dell’azione degli altri. Ciò è stato dimostrato usando il paradigma di osservazione dell’azione e l’fMRI. RIFERIMENTI BIBLIOGRAFICI Brand, G., & Millot, J. L. (2001). Sex differences in human olfaction: between evidence and enigma. Quarterly Journal of Experimental Psychology, 54, 259-270. Castiello, U. (1996). Grasping a fruit: selection for action. Journal of Experimental Psychology: Human Perception and Performance, 22, 582-603. Ecuyer-Dab, I., & Robert, M. (2004). Have sex differences in spatial ability evolved from male competition for mating and female concern for survival? Cognition, 91, 221-257. Gazzola, V., Aziz-Zadeh, L., & Keysers, C. (2006). Empathy and the somatotopic auditory mirror system in humans. Current Biology, 16, 1824-1829. Patchay, S., Castiello, U., & Haggard, P. (2003). A crossmodal interference effect in grasping objects. Psychological Bulletin Reviews, 10, 924-931. Zahariev M. A., & MacKenzie, C. L. (2007) Grasping at thin air: multimodal contact cues for reaching and grasping. Experimental Brain Research, 180, 69-84.

This thesis is a study of receptor-mediated events occurring in olfaction. Potential enzymes involved in olfactory transduction were investigated using standard biochemical techniques, and an investigation of the fatty acid receptor/s was attempted using psychophysical methods. 1. Other investigators in olfaction have recently demonstrated an odorant modulated adenylate cyclase in the frog. We have shown that tissue preparations from the rat have high levels of the enzyme adenylate cyclase. This activity was stimulated in the presence of odorants by up to two times the basal value. The concentrations of odorants used were in the range expected to be physiologically relevant. Both basal and stimulated adenylate cyclase were inhibited by μM calcium ion. Tissue preparations from brain showed no odorant activation. Guanylate cyclase was present at a tenth the concentration of adenylate cyclase and showed no odorant simulation. 2. There are no studies in the literature characterising the cyclic nucleotide phosphodiesterases in olfactory tissue. The Sutherland criteria require the presence of a cyclic nucleotide phosphodiesterase (PDE) in olfactory tissue, if cyclic AMP is to be a second messenger in olfaction. It is possible that olfactory PDE is directly regulated by a receptor, as is found in vision. It is important, therefore, that the PDE’s in olfactory tissue are characterised. Tissue preparations of the rat and sheep were shown to have high levels of cyclic nucleotide phosphodiesterase. The activities were not stimulated in the presence of physiologically relevant concentrations of odorants; inhibition of these activities by odorants was not significantly different from that of brain homogenates. Characterisation of the phosphodiesterase isoenzymes separated by DEAE chromatography established that they resembled the isoenzymes characterised from other tissues. The evidence presented indicates that olfactory tissue does not resemble visual tissue, which has a receptor-linked phosphodiesterase. All evidence suggests that PDE’s in olfactory tissue serve to return cyclic nucleotide concentrations to resting levels after stimulation. The observation that the Type 1 (calcium/calmodulin stimulated) phosphodiesterase is present in high concentrations in olfactory tissue suggests that calcium ion concentration in vivo may be an important regulator of phosphodiesterase activity. 3. The threshold values of various short chain fatty acids, of high purity, were determined using human subjects. The results were one order of magnitude greater than found by Amoore (1970) but showed a similar group trend. Descriptive analysis was also performed on these acids by generating a series of descriptors sufficient to discriminate between the acids. Analysis of the results by principal component analysis yielded a three dimensional map that showed the acids clustering into four groups. These four groups could indicate the presence of four receptors. Attempts to demonstrate structure-activity relationships between the thresholds, and descriptive analysis results with various physical and chemical parameters, failed. This was probably due to the interaction of the acids with more than one receptor. So far, the lack of success in identifying olfactory receptors by researchers has meant that investigations of olfactory receptors have had to be done using psychophysical techniques such as those used in this report. It will probably not be known if these methods are useful for identifying receptors, until the receptors can be purified and characterised biochemically.

This thesis examines the clinical and pathological involvement of the olfactory system in Parkinson’s Disease (PD). The main aim is to investigate the practical use of smell identification tests (SITs) in parkinsonism and tremor. A secondary objective is to investigate the pathological involvement of the rhinencephalon. Commercially available SITs were used to differentiate PD patients from control subjects in the UK, Brazil and Sri Lanka, showing SITs have combinations of sensitivity and specificity greater than 80%. Based on the data obtained a traffic light ruler was devised to determine the likelihood of a patient having PD at the time of the initial consultation. This was then used to interpret SITs in 34 patients with possible parkinsonism, showing 86.4% sensitivity and 80.0% specificity of SITs when compared to dopamine transporter imaging using single photon emission computed tomography (SPECT) as the gold-standard for detecting nigrostriatal dopamine denervation. Olfaction was shown to be severely impaired in parkinsonism related to LRRK2 mutations, moderately impaired in subjects with pure autonomic failure, multiple system atrophy and progressive supranuclear palsy (PSP) and normal in patients with essential tremor, dystonia and in subjects who had been diagnosed as having PD, but were found to have normal scans. This indicates that SITs will be more useful in differentiating PD from non-degenerative tremors than from atypical parkinsonism. Neuropathological changes were investigated in the rhinencephalon and it was demonstrated that α-synuclein accumulation in the primary olfactory cortex is heterogeneous, being more severe in the temporal subdivision of the piriform cortex. The piriform cortex had Lewy body pathology in all 10 PD cases studied, as well as in 7 control cases who presented incidental Lewy body pathology and four cases of LRRK2 related parkinsonism. The piriform cortex had abnormal tau accumulation in 6 PSP patients, suggesting tauopathy in the rhinencephalon is a possible substrate for hyposmia in PSP.

The primary aim of this thesis was to investigate, using functional magnetic resonance imaging (fMRI), the neurophysiological basis of multisensory integration involving smell and vision. To achieve this goal, several technical challenges had to be addressed: the attainment of sufficiently high quality fMRI images in olfactory brain regions within the orbitofrontal cortex (OFC), the construction of a stimulus delivery system adequate for rapid and controlled odour delivery in the MRI environment, and optimal strategies for delivering and perceiving liquid flavour stimuli in the scanner. In two initial fMRI experiments, strategies including sensitivity encoding and passive shimming to improve OFC image quality were explored. The results demonstrated that both methods can improve signal detection in OFC, a brain area particularly sensitive to susceptibility artefacts. In a further fMRI study, the effectiveness of two methods of delivering odorants dissolved in liquids was compared. In this study, the same set of participants was required to either swallow the liquid immediately after delivery or hold it in their mouths for a brief period of time. The results indicated that while both methods allowed detection of activity in primary olfactory and gustatory cortices, activation of the OFC was not observed when participants swallowed the liquids immediately. This was presumed to be due to the increased head motion associated with swallowing. Finally, the mechanisms underlying visual-olfactory integration were investigated using a combination of behavioural and imaging methods. An initial behavioural study revealed strong colour-odour associations for certain smells associated with fruits (e.g. lemon - yellow). In a subsequent fMRI study, volunteers were presented with a selection of the most colour-associated odours from the prior behavioural study either in isolation or in the presence of congruent and incongruent colours. Analysis of the fMRI data revealed that a highly left lateralised network of brain areas comprising of the OFC and insular showed increasingly stronger responses to odour-colour combinations of higher congruency. In a follow-up fMRI study, this same network was also found to be responsible for integrating odours, not only with colours, but also with their corresponding visual images (objects). In sum, the series of fMRI studies undertaken in this thesis argue for a fundamental role of the OFC in the integration of olfactory-visual inputs in the human brain.

Thesis (doctoral)--Ludwig-Maximilians-Universität München, 2008.
Title from PDF t.p. (viewed on Jan. 8, 2009). Some chapters co-authored with others. Includes bibliographical references (p. 117-127).

Tous les organismes vivants sont entourés de fluides, air ou eau, qui créent des paysages sensoriels uniques. Par exemple, les signaux chimiques se dispersent dans le fluide par diffusion et advection et lorsque l'écoulement est turbulent, la concentration d'odeurs se décompose en filaments et en taches discrètes d'intensité variable. Dans ma thèse, je me suis concentré sur la navigation olfactive dans des environnements turbulents et j'ai cherché de comprendre comment les organismes surmontent les incertitudes pour prendre des décisions. J'ai développé des simulations numériques (DNS) tridimensionnelles d'un écoulement turbulent dans un canal afin de recréer un environnement réaliste pour la recherche olfactive. J'ai réalisé ces simulations en personnalisant un open-source software appelé Nek5000, qui résout les équations de Navier-Stokes pour le champ de vitesse et l'équation d'advection-diffusion, qui régule l'évolution de l'odeur (scalaire passif) dans un fluide. Après avoir généré de grands ensembles de données de dynamique des fluides sur l'évolution des odeurs dans un canal, j'ai analysé quelles caractéristiques du signal olfactif sont les plus pertinentes pour localiser la source de l'odeur. Étonnamment, non seulement le signal, mais aussi son absence peut être informative pour déduire la distance de la source de l'odeur. En utilisant des algorithmes de Reinforcment Learning, j'ai montré que l'intensité de la concentration d'odeur est une mesure informative, mais que la dynamique temporelle du signal permet des prédictions robustes dans différentes conditions et à différentes distances de la source. Ces résultats théoriques suggèrent qu'il est avantageux sur le plan informatique de mesurer à la fois l'intensité et la dynamique de l'odeur. J'ai analysé un ensemble d'enregistrements neuronaux de souris éveillées, démontrant qu'elles sont bien capables de stocker les deux quantités, et que la représentation neuronale dépend du flux sous-jacent. J'ai alors considéré le problème de la navigation jusqu'à la source de l'odeur turbulente. Bien que les animaux (par exemple les papillons de nuit et les crustacés) effectuent cette tâche de manière robuste, les algorithmes qu'ils utilisent ne sont pas compris. J'ai modélisé la navigation olfactive en utilisant le cadre des Partially Observable Markov Decision Processes (POMDP) et j'ai proposé une théorie normative pour expliquer l'alternance entre renifler dans l'air et renifler le sol, typique des mammifères comme les rongeurs et les chiens. L'alternance découle de la physique des fluides, prescrivant que l'odeur près du sol est plus continue que dans l'air, mais reste relativement proche de la source. En revanche, au niveau du nez, l'odeur est transportée rapidement loin de la source, mais est plus bruyante et intermittente. Un agent recherchant la source de l'odeur doit donc renifler l'air lorsqu'il est loin de la source pour augmenter ses chances de détecter l'odeur. Une fois que l'agent a localisé le panache d'odeur, il doit continuer la recherche en reniflant le sol où la piste est moins intermittente. Le moment exact de l'alternance découle de la Marginal Value Theory. Enfin, le comportement communément observé chez les organismes recherchant une source d'odeur, procédant en cast et surge émerge spontanément de ce cadre computationnel
All living organisms are surrounded by fluids, either air or water, which create unique sensory landscapes. For example, chemical signals disperse in the flow by diffusion and advection and when the flow is turbulent odor concentration breaks up in filaments and discrete patches of varying intensity. In my thesis I focused on olfactory navigation in turbulent environments and I aimed at understanding how organisms overcome uncertainties to make decisions. I developed three-dimensional direct numerical simulation of a turbulent channel flow to recreate a realistic environment for olfactory search. I realized these state of the art simulations by customizing an open software called Nek5000, which solves the Navier-Stokes equations for the velocity field and the advection-diffusion equation, which regulates the evolution of the odor (passive scalar) in a fluid. After generating large fluid dynamics datasets of odorant evolution in a channel, I analyzed which features of the olfactory signal are more relevant to locate the odor source. Surprisingly, not only the signal, but also its absence can be informative to infer the distance from the odor source. Using supervised learning algorithms I showed that the intensity of odor concentration is an informative measure, but that the temporal dynamics of the signal allow robust predictions in different conditions and at different ranges from the source. These theoretical results suggest that it is computationally advantageous to measure both odor intensity and timing. I analyzed a set of neural recording from awake mice, demonstrating that they are indeed able to store both quantities, and that the neural representation depends on the underlying flow. I then considered the problem of navigating to the source of the turbulent odor. Although animals (for example moths and crustaceans) robustly perform this task, the algorithms they use are not understood. I modeled olfactory navigation using the framework of Partially Observable Markov Decision Processes (POMDP) and I proposed a normative theory to explain the alternation between sniffing in the air and sniffing the ground, typical of mammals like rodents and dogs. Alternation stems from the physics of fluids, prescribing that odor near the ground is more continuous than up in the air, but remains relatively close to the source. In contrast, at nose level the odor is transported quickly away from the source, but is more noisy and intermittent. An agent searching for the odor source should thus sniff in the air when it is far from the source to increase its chances of detecting the odor. Once the agent localizes the odor plume, it should continue the search sniffing the ground where the trail is less intermittent. The exact timing for alternation stems from marginal value theory. Finally, the commonly observed behavior of searchers proceeding in casts and surges emerges from this computational framework, and alternation naturally complements this dynamics to ensure optimal exploration

The present work, employing biochemical, biophysical and electrophysiological techniques, attempted to identify specific receptor sites in the vertebrate olfactory system for heterocyclic odorants. An in vitro rat preparation was developed and characterised for use in vapour-phase chemical modification experiments; the EOG responses obtained from this preparation were stable for up to 5 hours after the death of the animal. The signals to various compounds were differentially reduced when brominated odorants were employed as vapour-phase labelling reagents; the responses obtained to these derivatives and to their non-reactive analogues were preferentially diminished. The effect of concanavalin A on ECGs obtained from an in vivo frog preparation was examined. This lectin was found to preferentially inhibit the signals elicited by small, sweaty-smelling carboxylic acids; the responses to most of the non-carboxylic acid odorants tested were not significantly inhibited. The failure to identify specific receptor sites by electrophysiological techniques prompted the performance of odorant binding studies. Examinations of the interaction of [3H] 2-isobutyl-3- methoxypyrazine with 13,000 x g supernatant fractions of sheep olfactory epithelium showed that a component of the homogenate fraction exhibited high affinity saturable binding of this odorant (KD-10-8M). However, the presence of large amounts of non-specific binding, substantially decreased the sensitivity and accuracy of the assay. Non-specific binding was observed with tissue fractions of sheep respiratory epithelium, brain and liver. An investigation of binding specificity showed that other bell pepper odorants competed for the 2-iscbutyl-3-methoxypyrazine binding site. The steno requirements for the protein binding of various substituted heterocyclic odorants were examined using nuclear magnetic relaxation techniques. Model studies performed with bovine serum albumin showed that particular side chains of the odorants tested were primarily involved in the binding interaction. The methoxy group of 2-isopropyl-3-methoxypyrazine was found to be responsible for primary recognition by 13,000 x g supernatant fractions of sheep olfactory epithelium.

L’objectif de ce travail est de vérifier l’hypothèse selon laquelle les troubles olfactifs peuvent êtres des marqueurs de la dépression et différencier entre dépression unipolaire et dépression bipolaire. Dans ce projet, nous avons évalué et comparé les capacités olfactives de plusieurs groupes de sujets : patients en dépression unipolaire ou bipolaire, symptomatique ou en rémission, ainsi que des témoins sains. Nos résultats confirment la présence de marqueurs olfactifs d’état (seuil et mémoire olfactive, identification des odeurs), et de trait (jugement hédonique et émotionnel) de la dépression unipolaire et des marqueurs d’état (mémoire olfactive) et de trait (jugement hédonique et émotionnel, identification des odeurs et mémoire olfactive) de la dépression bipolaire. Nous avons aussi trouvé des marqueurs de différenciation des dépressions unipolaire et bipolaire (jugement hédonique). Il s’agit de la première étude différenciant la dépression unipolaire de la dépression bipolaire à travers les marqueurs sensoriels. D’autres études sont nécessaires afin de montrer l’utilité de l’olfaction dans la prise en charge des troubles de l’humeur
The objective of this research was to test the hypothesis that olfactory dysfunctions can constitute potential markers of depression, and that they help differentiating between unipolar and bipolar depression. In this project, we evaluated and compared the olfactory capacities of healthy controls and patients with unipolar and bipolar depression, in symtpomatic phases and in rémission. Our results confirmed the presence of state (olfactory threshold, olfaction memory and identification) and trait (hedonic and emotional ratings) markers of unipolar depresison and state (olfactory memory) and trait (hedonic and emotional rating, olfactory memory and identification) markers of bipolar depression. We identified an olfactory marker differentating between unipolar and bipolar depression (hedonic rating). This is the first study differentating unipolar depression from bipolar one through a sensory marker. Further studies are needed to show the utility of olfaction in the treatment of mood disorders

The detection of low level concentrations of particles in a gaseous environment is of importance to many fields, especially Homeland Security. The ability to identify ppb concentrations of explosives and their degradation products can aid in the detection of improvised explosive devices (IEDs), ammunition dumps, or hidden explosives. One method of accomplishing this task is through the use of an array of chemiresistors in an electronic nose device. For this study, chemiresistors were constructed using 3-D silica nanospring mats with a contiguous film of ZnO nanocrystals and ZnO nanocrystals decorated by metallic nanoparticles. Samples with an average grain size of 15nm were found to be the most responsive and upon exposure to a gas flow of 20% O2 and 80% N2 with ~200 ppm of acetone and an operational temperature of 400 oC produced a relative change in conductance by a factor of 400. The addition of metal nanoparticles onto the surface of the ZnO nanocrystals produced a relative change in conductance by a factor of 1100. Under optimum conditions, sensing elements of this design exhibited well-defined spikes in conductance upon exposure to explosive vapors (TNT, TATP) at the ppb levels. The use of a pattern recognition system allowed discrimination between three analyte chemicals.

La vision est certainement le sens le plus développé chez les rapaces, souvent cités comme les vertébrés possédant la plus grande acuité visuelle. Pourtant, les rapaces figurent parmi les victimes les plus fréquentes des collisions avec des éoliennes et autres dispositifs anthropiques. Etant donné les enjeux de conservation et le coût des opérations de conservation, il est indispensable de mieux comprendre comment les capacités sensorielles des rapaces affectent leur technique de recherche alimentaire et les interactions avec les dispositifs anthropiques (par exemple jusqu’à quelle altitude/distance les vautours peuvent-ils être détecter les charniers et les obstacles potentiels et comment optimiser les mesures de gestion des habitats ?). En ce qui concerne l'olfaction, le postulat ancien que les oiseaux en général ont une olfaction quasi nulle est réfuté grâce à la publication récente d’expériences qui montrent le contraire chez plusieurs espèces d’oiseaux, des passereaux aux oiseaux marins. L’olfaction est-elle vraiment un sens « manquant » chez les rapaces? Pourquoi seuls les vautours américains auraient-ils développé un sens aigu de l’olfaction ? Notre projet d’étude de l’écologie sensorielle des rapaces repose principalement sur de test de conditionnement avec renforcement, conduits sur des oiseaux issus de plusieurs parcs zoologiques de France. L’originalité de notre projet serait de combiner des expériences de vision et d’olfaction, sur une grande diversité d’espèces (Vautours, Buses, Milans), d’origine phylogénétique, de régimes alimentaires et de technique de recherche alimentaire différents, à la fois au sol et en vol. La première étape aura lieu en conditions contrôlées en volières, avec des expériences de conditionnement opérant après dressage : réponses des oiseaux à différents stimuli visuels et odeur. Dans un deuxième temps des expériences en vol pourront être menées, sur des oiseaux dressés à effectuer des vols libres, dont les mouvements précis peuvent être suivis en 3 dimensions par des balises GPS couplées à des accéléromètres et des caméras vidéos. Il serait alors possible de connaître précisément les capacités sensorielles utilisées pour la recherche alimentaires de chaque espèce et d’analyser les comportements de vol en lien avec l'aérologie
The vision is certainly the most developed sense in raptors, and these birds are cosidered as the vertebrates with the greatest visual acuity. However, raptors are among the most frequent victims of collisions with wind turbines and other human features. Given the conservation issues and the cost of conservation operations , it is essential to understand how sensory abilities of raptor affect their foraging ecology and interactions with human features (eg at which altitude / distance vultures can detected graves and potential obstacles and how optimize the measure of habitats management). But vision is not the only sense that raptor may have. Olfaction in birds was historically neglected, but recent evidence suggests that many bird species, from passerines to seabirds, use olfaction. Consequently, it make sense that olfaction may lead some behaviours in raptor too. To date however olfaction has been searched and shown only in the American vultures. Our project aims to study the sensory ecology of raptors based primarily on captive animals and condition protocols. The originality of our project is to combine the experience of vision and olfaction, on a wide variety of raptor species present in French zoos, with different phylogenetic origin, diets, and different foraging ecologies. The first step will takes place under controlled aviaries conditions, with operant conditioning experiments: responses of birds to different visual and odor stimuli. In a second phase, flight experiments will be conducted on birds trained to perform free flights, whose precise movements can be tracked in three dimensions by GPS tags coupled with accelerometers and cameras videos. It would then be possible to determine precisely the sensory capabilities used for food research for each species, and analyze the flight behaviour with respect to aerology

Le neuropeptide somatostatine est largement exprimé dans le cerveau et son rôle modulateur via ses six récepteurs est bien établi dans les fonctions neuroendocriniennes et cognitives. La présence de la somatostatine et de ses récepteurs dans le système olfactif, et leur déclin dans plusieurs maladies neurodégénératives associées à des troubles précoces du sens de l’odorat, suggèrent que ce peptide participe au traitement de l’information olfactive. Notre travail démontre que, dans le bulbe olfactif de souris, la somatostatine est exprimée par des interneurones de van Gehuchten précisément situés dans la partie interne de la couche plexiforme externe. Ces interneurones sans axone établissent des synapses dendrodendritiques réciproques avec les dendrites latérales des cellules de projection du bulbe, les cellules mitrales. En agissant sur les récepteurs sst2 exprimés par leurs dendrites, la somatostatine influence la transmission synaptique dendrodendritique entre cellules principales et cellules granulaires qui est l’origine d’oscillations gamma dans le réseau neuronal bulbaire (40-100 Hz). Les variations de la puissance de ces oscillations induites par le blocage ou l’activation du récepteur sst2 sont associées à des modifications du seuil de discrimination olfactive. Ainsi, nos résultats démontrent que la libération endogène de somatostatine participe à la modulation des oscillations gamma bulbaires et à la discrimination olfactive. Ce travail ouvre donc des perspectives sur l’implication de la somatostatine dans le traitement de l’information sensorielle et dans le fonctionnement des réseaux neuronaux du télencéphale.

L'activité du bulbe olfactif (BO) de mammifère repose sur divers contrôles : périphérique, central et intrinsèque aux BO, associés à une activité électrophysiologique dans les bandes de fréquence θ (2-10Hz), β (15-30Hz) and γ (30-90Hz). Cependant ces activités résultantes, temporellement stéréotypées restent à comprendre sur les plans biophysiques et fonctionnels. L'implication des synapses dendrodendritiques entre cellules mitrales (CMs, les neurones de projection du BO) et cellules granulaires (CGs, les interneurones locaux) dans ces rythmicités nous a conduits à explorer de façon extensive les différentes propriétés de ces interactions dans la dynamique cellulaire et bulbaire. L'approche computationnelle s'est révélé un outil efficace pour l'étude des mécanismes à ces différents niveaux. Nous avons d'abord montré que l'inhibition shuntante sur les dendrites latérales des CMs pouvait contrôler la stabilité de décharge des CMs. Un tel processus contrôle la synchronisation de l'activité dans le BO, une propriété majeure pour la transmission de l'information aux structures corticales. Ensuite nous avons montré dans un réseau de CMs et CGs que le mode d'activation et les interactions synaptiques contrôlaient la dynamique oscillatoire. Dans le cas d'interactions fortes, l'activité des CMs peut se synchroniser sur chaque cycle d'oscillations qui couvrent plutôt la bande de fréquence β. Enfin, en s'appuyant sur des données expérimentales issues du rat anesthésié, nous avons montré que pendant les oscillations γ du potentiel de champ local, l'activité des CMs pouvaient se phaser par rapport à l'oscillation conduisant à une stabilité des phases et du taux de décharge. Le mécanisme sous-jacent fondé sur des entrées synaptiques faibles oscillantes à la fréquence γ pourrait conduire à un mécanisme d'auto-synchronisation et ainsi expliquer l'émergence de bouffées d'oscillations γ. Les corrélats dynamiques et comportementaux associés aux oscillations γ et β suggèrent que ces activités pourraient être associées à la perception d'ensemble et la segmentation des odeurs, deux des fonctions principales du système olfactif
Mammalian olfactory bulb (OB) activity displays electrophysiological activity in different frequency bands: θ (2-10Hz), β (15-30Hz) and γ (30-90Hz). The resultant stereotypical temporal activities remain to be understood in terms of biophysical dynamics and functionality. We here studied the functional role of dendrodendritic synapses between mitral cells (MC), the output neurons of the OB and granule cells (GC), a type of local interneurons, in these oscillatory regimes. To this end, the computational modeling approaches were employed. We first show that shunting inhibition on the MC lateral dendrite is able to influence the timing of MC discharge. This process could regulate synchrony among MCs, considered an important property of information transmission to OB downstream structures. Second, in a network of MCs and GCs, we showed that synaptic interactions and sensory stimulation can influence oscillatory dynamics. In the case of strong network connectivity, the MCs could robustly synchronize in a β frequency range. Third, using experimental data from anesthetized rat, we showed that during γ local field potential oscillation, the phase of MC spikes could lock with the oscillation leading to some stabilized phases and firing rates. The underlying mechanism, based on weak γ-oscillatory synaptic input and MC intrinsic properties could lead to a self-synchronization process in the bulb and explain the emergence of γ bursts during olfactory stimulation. Dynamical and behavioral correlates of γ and β oscillations suggest they could be associated with perception and segmentation of odors, the two major functions of the olfactory system

Comment les odeurs contrôlent-elles le comportement animal ? Dans ma thèse, j'ai utilisé des manipulations optogénétiques et chimiogénétiques in vivo de l'activité neurale combinées à des analyses comportementales pour explorer l'organisation de circuits cérébraux impliqués dans des comportements olfactifs chez la souris. J'ai mis au point un test de conditionnement aversif olfactif indépendant de l'intensité des odeurs. J'ai démontré que les souris pouvaient généraliser une réponse aversive en présentant différentes concentrations d'odeurs. J’ai ensuite testé si les souris pouvaient apprendre cette tâche en inactivant les interneurones exprimant la parvalbumine dans le cortex olfactif (piriforme). J'ai trouvé que l’inactivation des cellules PV, n'était pas suffisante pour abolir l'aversion aux odeurs acquise, ce qui suggère que des composants de circuits neuronaux supplémentaires contribuent à la perception de l'odeur indépendamment de sa concentration. Ensuite, j'ai tenté de comprendre la constitution relative des différentes voies neurales du piriforme dans ce comportement d’aversion apprise. À l'aide d'outils génétiques et viraux, j'ai ciblé des sous-populations distinctes de neurones piriformes, et j'ai constaté que l'activité neurale induite par la lumière dans les cellules du piriforme projetant vers le bulbe olfactif et vers le cortex préfrontal, mais pas dans les cellules du piriforme projetant vers l’amygdale corticale et vers le cortex entorhinal latéral était suffisante pour supporter le conditionnement aversif. Ces résultats contribuent à mieux comprendre les propriétés fonctionnelles des circuits neuronaux corticaux pour l'olfaction
How do odors control animal behavior ? In my thesis, I have used in vivo optogenetic and chemogenetic manipulations of neural activity combined with behavioral analyses to explore the organization of brain circuits involved in olfactory behaviors in mice. In the first part of the thesis, I established an odor intensity-independent olfactory conditioning task. I demonstrated that mice were able to generalize a learned escape behavior across a range of different odor concentrations. I then tested if by silencing Parvalbumin-expressing interneurons in the olfactory (piriform) cortex, a candidate cell population for mediating odor concentration invariance, mice would fail to learn the task. I found that silencing PV cells was not sufficient to abolish learned aversion, suggesting that additional neural circuit components contribute to concentration-invariant odor perception. Next, I asked whether different piriform neural output pathways differed in their ability to support learned aversion. Using viral-genetic tools, I targeted distinct subpopulations of piriform neurons and I found that light-induced neural activity in only piriform principle cells could drive a behavioral response. Furthermore, I tested the sufficiency of subpopulations of piriform projection neurons to drive learned aversion. I found that photostimulation of olfactory bulb- and prefrontal cortex-projecting piriform neurons was sufficient to support aversive conditioning, but not the photostimulation of cortical amygdala- and lateral entorhinal cortex-projecting piriform neurons. Together, these results provide new insights into the functional properties of cortical neural circuits for olfaction

L'objectif de cette thèse est d'utiliser MEMRI (manganese-enhanced magnetic resonance imaging) pour étudier le traitement d'odeurs signifiantes dans le cortex olfactif primaire de rats dans les conditions les plus proches de la perception naturelle. MEMRI est une méthode fondée sur la détection d'un agent de contraste fonctionnel et rémanent de l'activité neuronale, le manganèse, qui a prouvé son efficacité pour montrer le traitement différencié d'odeurs dans le bulbe olfactif chez l'animal vigile. Cependant, cette technique a été surtout utilisée pour tracer les voies neuronales, mais relativement peu pour explorer des fonctions sensorielles. C'est pourquoi nous avons conduit deux études visant l'une à définir les conditions d'application du manganèse et l'autre à optimiser le traitement des images MEMRI, avant d'aborder la question biologique proprement dite. S'appuyant sur ces développement méthodologiques, nous avons ensuite utilisé MEMRI pour étudier les variations du traitement d'odeurs signifiantes (odeurs de nourriture et de prédateur comparées à une situation de contrôle) dans le cortex olfactif primaire de rats. Nous avons montré que le traitement cérébral d'une odeur de prédateur est différent de celui de la situation de contrôle dans le cortex olfactif primaire. Nous avons confirmé ce résultat par immunomarquage Fos dans le cortex piriforme. Mis ensemble, les résultats de MEMRI et Fos suggèrent que le traitement cérébral d'une odeur peut varier en terme de taille de populations de neurone recrutés ainsi qu'en termes d'intensité de l'activation de ces neurones. Enfin, les résultats MEMRI montrent qu'un message olfactif crucial, pour la survie, est traité asymétriquement dans le cerveau. Les avancées méthodologiques et scientifiques qu'apporte cette thèse ouvrent la voie à une meilleure compréhension du traitement cérébral des odeurs.

Chez l'homme comme chez l'animal, les odeurs guident le comportement et motivent à agir. La valeur hédonique (le caractère plus ou moins plaisant) est la dimension olfactive principale et est généralement utilisée pour décider d'approcher ou fuir la source odorante. Bien que cette attractivité soit façonnée par l'expérience, certaines odeurs non-familières sont spontanément attractives ou répulsives. Le caractère plus ou moins plaisant d'une odeur serait, du moins en partie, inné. Il existerait ainsi une signature neurale spécifique de la valeur hédonique des odeurs, et c'est ce que cette thèse s'emploie à identifier.Après sélection d'odorants spontanément plus ou moins attractifs (plaisant et déplaisants respectivement), nous avons recherché les bases neurales qui sous-tendent ces comportements. Nous avons tout d'abord cartographié (expression de Zif268) puis manipulé (optogénétique) l'activité neuronale du bulbe olfactif en réponse à ces odorants, et avons révélé une signature neurale bulbaire de la valeur hédonique des odeurs le long de l'axe antéro-postérieur.Puis, afin d'analyser comment le message hédonique était interprété par les aires olfactives et associatives supérieures, nous avons développé une méthode de recalage de l'activité cérébrale dans un atlas de référence, assurant une cartographie rapide, précise et fiable de cette activité. Enfin, en combinant cette méthode à des approches comportementales, électrophysiologiques et pharmacologiques, nous avons montré un rôle du système de la récompense dans le codage de la valeur hédonique des odeurs et qu'une odeur peut être perçue comme une récompense, motivant alors les comportements d'approche et de retrait
In humans and animals, odors guide behavior and motivate action. The hedonic value (that is the pleasantness) is the main olfactory dimension and is generally used to decide to approach the odor source or move away. While this attractiveness is shaped by experience, some unfamiliar odors are spontaneously attractive or repulsive. The pleasantness of an odor would be, at least in part, innate, and suggest a specific neural signature of the hedonic value of odors. The global aim of this thesis is to decipher neuronal mechanisms underlying the hedonic value of odors.After having selected odorants with various level of attraction (pleasant and unpleasant), we have deciphered the neural bases that underlie these behaviors.We first mapped (expression of Zif268) and then manipulated (optogenetic) the neuronal activity of the olfactory bulb in response to these odors, and have revealed a bulbar neural signature of the hedonic value of odors along the antero-posterior axis.Then, in order to analyze how the hedonic information was interpreted by the higher olfactory and associative areas, we developed a method allowing the registration of brain activity in a reference atlas, that ensure a fast, accurate and reliable mapping of this activity. Finally, by combining this method with behavioral, electrophysiological and pharmacological approaches, we have shown a role of the reward system in the coding of odor hedonics and that an odor can act as a reward, thus motivating behavior, approach and withdrawal

The thesis falls into the field of machine olfaction and accompanying experimental set up for chemical gas sensing. Perhaps more than any other sensory modality, chemical sensing faces with major technical and conceptual challenges: low specificity, slow response time, long term instability, power consumption, portability, coding capacity and robustness. There is an important trend of the last decade pushing artificial olfaction to mimic the biological olfaction system of insects and mammalians. The designers of machine olfaction devices take inspiration from the biological olfactory system, because animals effortlessly accomplish some of the unsolved problems in machine olfaction. In a remarkable example of an olfactory guided behavior, male moths navigate over large distances in order to locate calling females by detecting pheromone signals both rapidly and robustly. The biomimetic chemical sensing aims to identify the key blocks in the olfactory pathways at all levels from the olfactory receptors to the central nervous system, and simulate to some extent the operation of these blocks, that would allow to approach the sensing performance known in biological olfactory system of animals. New technical requirements arise to the hardware and software equipment used in such machine olfaction experiments. This work explores the bioinspired approach to machine olfaction in depth on the technological side. At the hardware level, the embedded computer is assembled, being the core part of the experimental set up. The embedded computer is interfaced with two main biomimetic modules designed by the collaborators: a large-scale sensor array for emulation of the population of the olfactory receptors, and a mobile robotic platform for autonomous experiments for guiding olfactory behaviour. At the software level, the software development kit is designed to host the neuromorphic models of the collaborators for processing the sensory inputs as in the olfactory pathway. Virtualization of the set up was one of the key engineering solutions in the development. Being a device, the set up is transformed to a virtual system for running data simulations, where the software environment is essentially the same, and the real sensors are replaced by the virtual sensors coming from especially designed data simulation tool. The proposed abstraction of the set up results in an ecosystem containing both the models of the olfactory system and the virtual array. This ecosystem can loaded from the developed system image on any personal computer. In addition to the engineering products released in the course of thesis, the scientific results have been published in three journal articles, two book chapters and conference proceedings. The main results on validation of the set up under the scenario of robotic odour localization are reported in the book chapters. The series of three journal articles covers the work on the data simulation tool for machine olfaction: the novel model of drift, the models to simulate the sensor array data based on the reference data set, and the parametrized simulated data and benchmarks proposed for the first time in machine olfaction. This thesis ends up with a solid foundation for the research in biomimetic simulations and algorithms on machine olfaction. The results achieved in the thesis are expected to give rise to new bioinspired applications in machine olfaction, which could have a significant impact in the biomedical engineering research area.
Esta tesis se enmarca en el campo de bioingeneria, mas particularmente en la configuración de un sistema experimental de sensores de gases químicos. Quizás más que en cualquier otra modalidad de sensores, los sensores químicos representan un conjunto de retos técnicos y conceptuales ya que deben lidiar con problemas como su baja especificidad, su respuesta temporal lenta, su inestabilidad a largo plazo, su alto consumo enérgético, su portabilidad, así como la necesidad de un sistema de datos y código robusto. En la última década, se ha observado una clara tendencia por parte de los sistemas de machine olfaction hacia la imitación del sistema de olfato biológico de insectos y mamíferos. Los diseñadores de estos sistemas se inspiran del sistema olfativo biológico, ya que los animales cumplen, sin apenas esfuerzo, algunos de los escenarios no resueltos en machine olfaction. Por ejemplo, las polillas machos recorren largas distancias para localizar las polillas hembra, detectando sus feromonas de forma rápida y robusta. La detección biomimética de gases químicos tiene como objetivo identificar los elementos fundamentales de la vía olfativa a todos los niveles, desde los receptores olfativos hasta el sistema nervioso central, y simular, en cierta medida, el funcionamiento de estos bloques, lo que permitiría acercar el rendimiento de la detección al rendimiento de los sistemas olfativos conociodos de los animales. Esto conlleva nuevos requisitos técnicos a nivel de equipamiento tanto hardware como software utilizado en este tipo de experimentos de machine olfaction. Este trabajo propone un enfoque bioinspirado para la ¿machine olfaction¿, explorando a fondo la parte tecnológica. A nivel hardware, un ordenador embedido se ha ensamblado, siendo ésta la parte más importante de la configuración experimental. Este ordenador integrado está interconectado con dos módulos principales biomiméticos diseñados por los colaboradores: una matriz de sensores a gran escala y una plataforma móvil robotizada para experimentos autónomos. A nivel software, el kit de desarrollo software se ha diseñado para recoger los modelos neuromórficos de los colaboradores para el procesamiento de las entradas sensoriales como en la vía olfativa biológica. La virtualización del sistema fue una de las soluciones ingenieriles clave de su desarrollo. Al ser un dispositivo, el sistema se ha transformado en un sistema virtual para la realización de simulaciones de datos, donde el entorno de software es esencialmente el mismo, y donde los sensores reales se sustituyen por sensores virtuales procedentes de una herramienta de simulación de datos especialmente diseñada. La propuesta de abstracción del sistema resulta en un ecosistema que contiene tanto los modelos del sistema olfativo como la matriz virtual . Este ecosistema se puede cargar en cualquier ordenador personal como una imagen del sistema desarrollado. Además de los productos de ingeniería entregados en esta tesis, los resultados científicos se han publicado en tres artículos en revistas, dos capítulos de libros y los proceedings de dos conferencias internacionales. Los principales resultados en la validación del sistema en el escenario de la localización robótica de olores se presentan en los capítulos del libro. Los tres artículos de revistas abarcan el trabajo en la herramienta de simulación de datos para machine olfaction: el novedoso modelo de drift, los modelos para simular la matriz de sensores basado en el conjunto de datos de referencia, y la parametrización de los datos simulados y los benchmarks propuestos por primera vez en machine olfaction. Esta tesis ofrece una base sólida para la investigación en simulaciones biomiméticas y en algoritmos en machine olfaction. Los resultados obtenidos en la tesis pretenden dar lugar a nuevas aplicaciones bioinspiradas en machine olfaction, lo que podría tener un significativo impacto en el área de investigación en ingeniería biomédica

This thesis recognizes that: in many systems the initial small molecule - receptor recognition processes, and thus signal transduction, is not fully understood to the highest level of scientifc explanation and prediction. One such example of this is olfaction. Molecules cannot necessarily be predicted from a smell, and similarly a smell from molecules. Better understanding of these initial steps, would have important repercussions, especially in the field of rational drug design. So in general the thesis proves the physical feasibility and potential of a novel and generic signaling model, and in particular looks at those processes in olfaction. The conjecture 'Could humans recognize odours through phonon assisted tunneling?' is tested. This is based on the idea (Turin, 1996) that the nose recognizes an odorant's vibrations (phonons) via inelastic electron tunneling (IETS). The nose thus acts as a 'meat spectroscope'. First the background biology of the olfactory system is evaluated, then the conjecture is posed as a soluble problem. Traditional physics ideas are reconciled with the biological environment. It is proven that no physics based objections hold against the working of this new mechanism, thus a predictive and explanatory theory is now introduced to the field. The parameters of odorant discrimination are explored. In particular the 'Huang-Rhys factor' is modeled as a measure of the electron-phonon coupling integral to signal transduction. Several approaches are considered, 'odorant spectra' is created. Objections to the conjecture are considered, in particular the apparent paradox of enantiomer discrimination. The apparent paradox is shown to be obsolete. A correlation between a certain type of flexibility and whether enantiomer pairs smell the same is found. A rule is established: The members of an enantiomer pair will smell alike (type 1) when the molecules are rigid, and will smell different (type 2) when they are flexible. This flexibility refers to a particular property of six-membered rings. A consequence of this finding leads to the investigation of certain steroids in correlation to their bio-effects, and it is found that similar features are apparent, thus the mechanism of biological IETS is applied to other systems.

Within the discipline of sociology human olfaction is rich with social significance yet remains a poorly charted frontier. Therefore, the following discourse is aimed toward the development of a foundation for the sociological study of olfaction. It is formed by the dual goals of unearthing the social history of olfaction and of providing a viable sociological account of the manner in which smells affect human ontology. From these goals arise the following research questions: (1) Have the meaning and social relevance of odors and the olfactory sensorium changed throughout different periods of history?; (2) How have those in the lineage of eminent sociological thinkers addressed the phenomenon of human olfaction during these periods?; and (3) What is the process by which aromatic stimuli are transformed from simple chemical compounds, drifting in the atmosphere, into sensations in a sensory field and then on to perceived objects, to subjects of judgment and interpretation, and finally to bases of knowledge which form and continually reform individuals in the world? The weaving of the sociohistorical tapestry of smell is undertaken to provide examples from thousands of years lived experiences as to the fluid and sociologically complex nature of individuals' olfactory senses. This historical information is presented in a narrative format and is synthesized from data gleaned from books, advertisements, articles in popular non-scientific magazines, as well as from the findings of studies published in medical/neurological, psychological, anthropological, and sociological scholarly journals. Regarding theoretical aim of this discourse, insights are drawn from Maurice Merleau-Ponty's phenomenological theory of human perception for the generation of a framework for the sociological study of olfaction. Merleau-Ponty's theoretical notions are modified, modernized, and refitted to more specifically fit the subject of human olfaction and to include all that has been discovered about the biological specifics of olfactory perception since the time of his writing. Taken in sum, this effort is an access point to the understanding of how olfactory sensory perceptions flow toward the ontological unfolding of individuals.

Olfactory signals are generally regarded as the oldest and most widespread form of communication across taxa. They can play an important role in the mediation of social interactions, reproductive status and warning of danger, whilst also signalling more fixed genetic factors such as the major histocompatability complex, which is linked to inbreeding avoidance. Little is known of the role odour might play in humans, although there is some indication that humans may be influenced by a family of androgen steroids called the 16-androstenes, produced in axillary odour. Here I aim to identify the role of androstene compounds in humans, as well as body odour as a whole, using two theoretical frameworks based on intersexual and intrasexual signalling. Evidence is found to suggest androstadienone (“AND”, a putative male pheromone) and male odour (a composite sample of axillary sweat) may be having a suppressive effect on males. Men exposed to AND feel less attractive and potentially behave less attractive too, as judged by third-party raters. In a physical performance test, male odour is found to have a similar suppressing effect, with exposure being linked to decreased men’s performance in a cycling time trial and aspects of a 30-second cycling sprint test. In contrast, women exhibited stimulatory responses to the male odour, not AND. An analytical assessment of male odour was carried out, in an effort to link androstene profiles to aspects of phenotypic quality and socially relevant traits. Cluster analysis revealed that men’s odour profiles fell into two groups, which in turn could be explained by relationship status. In essence, single men have different compounds in their odour to men in a relationship. Furthermore, the odour of single men appears to be preferred by women. Exposure to solutions based on these two groups had sex specific effects on the receiver. In conclusion, the results highlight the novel possibility of human male intra-sexual signalling, whilst providing the only empirical evidence of odour chemistry links with social function in humans; paving the way for further investigations in this field.

L’une des originalités du bulbe olfactif (BO), la seule structure relais entre la périphérie et le cortex, est le renouvellement permanent de ses interneurones chez l’adulte. À première vue, ce phénomène ne semble pas jouer de rôle important car seule une minorité des neurones nouvellement générés survivent. Lors d’une première étude, nous avons démontré l’existence d’une période critique dans la vie des nouveaux interneurones granulaires du BO adulte, au cours de laquelle leur survie peut être modulée. En fonction de l’âge du neurone, une période d’entraînement à la discrimination olfactive a augmenté, diminué ou n’a eu aucun effet sur la survie neuronale. La survie et l’élimination neuronales sont contrôlées par l’activité de manière différentielle, non seulement en fonction de l’âge du neurone, mais également de sa position spatiale. Dans une deuxième étude, nous avons montré qu’un taux normal d’élimination neuronale était crucial pour une exploration et une discrimination olfactives optimales. Le renouvellement des nouveaux neurones est précisément contrôlé : l’élimination et la sélection neuronales sont des processus actifs essentiels pour optimiser les performances olfactives. Nos travaux démontrent que la mort cellulaire programmée possède un rôle et n’est pas un simple mécanisme homéostatique qui permet de contrôler le nombre de neurones dans les circuits neuronaux bulbaires. La neurogenèse adulte pourrait donc permettre d’ajuster le fonctionnement du réseau neuronal bulbaire, en fonction des situations rencontrées.

Les techniques modernes d'imagerie fonctionnelle du cerveau utilisent le métabolisme cérébral comme marqueur d'activité neuronale. En effet le cerveau dépend intimement des apports sanguins en métabolites pour son fonctionnement. Cependant les mécanismes de régulation du métabolisme sont encore mal connus. Dans cette étude nous avons utilisé le modèle du bulbe olfactif chez le rat anesthésié pour caractériser la consommation d'oxygène en réponse à une stimulation physiologique. La quantification précise de la vascularisation du bulbe olfactif a pu mettre en évidence que la couche glomérulaire, très dense en synapses, est l'une des zones les plus vascularisées du cerveau. Cette couche est aussi le lieu d'une intense consommation d'oxygène lors du traitement de l'information olfactive. Par contraste, la couche du nerf, complètement dénuée d'interactions synaptiques et très peu vascularisée, consomme peu d'oxygène. L'étude pharmacologique de ces réponses métaboliques nous a permis de montrer que le compartiment post-synaptique du glomérule est le siège de cette intense activité métabolique. Cette dernière est aussi dépendante du traitement de l'information olfactive qui est effectué à la fois dans le bulbe olfactif et à la périphérie, dans la cavité nasale. Ceci nous a permis de caractériser l'effet de l'adaptation périphérique sur la consommation d'oxygène et le traitement local de l'information olfactive. Enfin, nous avons décrit en détail l'importance des phénomènes de diffusion au niveau du réseau microvasculaire dans le rééquilibrage transitoire du taux d'oxygène local.

L’alimentation maternelle conditionne la santé métabolique et cardiovasculaire de la progéniture, mais l’impact sur les systèmes sensoriels reste peu étudié. L’olfaction joue un rôle comportemental crucial pour l’évitement des dangers et pour la prise alimentaire. Dès le plus jeune âge, les odeurs participent à l’établissement des préférences alimentaires, qui influencent les habitudes alimentaires de l’adulte. Le système olfactif repose sur le fonctionnement de neurones qui se développent pendant la vie embryonnaire, continuent leur maturation après la naissance et sont continuellement régénérés au cours de la vie. Ces neurones sont en permanence modulés par les facteurs métaboliques. Les patients atteints de troubles métaboliques ont plus de risques de présenter des altérations de la perception des odeurs, et l’exposition à une alimentation de type obésogène ou diabétogène induit des perturbations olfactives chez le rongeur.Le but de cette thèse était d’explorer les effets d’une exposition périnatale au gras et au sucre, à travers l’alimentation maternelle pendant les périodes de préconception, gestation et lactation, sur la physiologie olfactive de souris juvéniles.L’alimentation grasse et sucrée (high-fat high-sucrose, HFHS) a modifié la composition lipidique du lait maternel. La caractérisation métabolique des petits a révélé un surpoids, un excès de masse grasse épididymaire et une hyperleptinémie chez les petits provenant d'une mère sous alimentation HFHS. Les capacités olfactives évaluées lors d'un test de nourriture enfouie et par mesure du comportement de flairage induit par les odeurs étaient altérées chez les petits dont la mère a été exposée à l'alimentation HFHS. Cependant, nos résultats n’ont pas montré de modification de la sensibilité de l’épithélium olfactif (EO) ou de l’expression des gènes codant pour les éléments de la cascade de transduction olfactive. L’exploration du traitement central du signal olfactif a révélé un impact de l’alimentation maternelle HFHS sur le degré de ramification dendritique des interneurones du bulbe olfactif. En revanche, l’activation des neurones dans le cortex piriforme après une exposition odorante n’était pas modifiée.Ainsi, l'alimentation maternelle HFHS pendant les périodes de développement des petits induit chez les mâles des altérations de la perception olfactive, sans perturbation de la détection des odeurs par l'EO, mais associées à des modifications neuronales dans les structures olfactives centrales. La leptine, hormone métabolique connue pour son action sur l’olfaction et sur le développement neuronal, pourrait être à l’origine de ces déficits olfactifs
The influence of maternal diet on progeny’s health has been thoroughly investigated regarding metabolic and cardiovascular diseases, but the impact on sensory systems remains unknown. Olfaction is of great behavioral importance for avoiding hazards and for feeding behavior. In childhood especially, olfaction participates in establishing food preferences, which partly determine adult eating habits. The olfactory system is made of sensory neurons that develop during the embryonic life, pursue their maturation after birth and are continuously regenerated over life. Olfactory neurons activity can be modulated by metabolic factors. Patients with metabolic disorders are at risk of impaired olfactory sensitivity. Adult mice exposed to an obesogenic or diabetogenic diet exhibit disrupted olfactory behavior.The aim of this thesis was to investigate the effect of a perinatal exposure to fat and sugar, through maternal diet during preconception, gestation and lactation, on the olfactory system of young mice.Maternal high fat high sugar (HFHS) diet modified milk lipids composition. When investigating pups’ metabolic phenotype, overweight, increased epididymal fat and hyperleptinemia were revealed in pup’s born from dams fed with the HFHS diet. Olfactory abilities were assessed in a buried food test and by measuring odor-induced sniffing behavior and were disrupted in the progeny of HFHS diet fed dams. However, olfactory epithelium sensitivity and gene expression of constituents of the olfactory transduction cascade were not affected by maternal HFHS diet. When investigating olfactory central processing, dendritic complexity of interneurons in the olfactory bulb was found to be affected by maternal HFHS diet. Meanwhile, neuronal activation in piriform cortex was not altered.These results show that maternal HFHS diet during pups’ development alters olfactory perception in male progeny, without impairing odor detection by the OE, and associated with neuronal modifications in olfactory central areas. Leptin is a metabolic hormone known to influence olfaction and neurons development which could have induced the olfactory defects

Dans une société allant de l'avant et voulant couper avec son côté animal, la perception olfactive a été jugée inutile et limitée à sa plus simple expression. Il n'est donc pas étonnant que la perception olfactive soit une des dimensions de notre univers sensoriel les plus difficiles à appréhender. Cette thèse de doctorat étudie la perception des odeurs chez l'Homme. La recherche s'est centrée sur deux aspects importants de l'odorat : la valence hédonique de l'odeur (son caractère agréable ou désagréable) et la qualité de l'odeur (par exemple, son caractère floral ou fruité). L'olfaction a également pour caractéristique d'être très variable d'un individu à l'autre. En effet, bien que certaines odeurs soient perçues de la même manière par la majorité de la population, de nombreuses autres sont perçues de manière très différente entre individus. Ainsi, le principal objectif de la thèse a été d'apporter des éléments d'explication des facteurs déterminant la variabilité interindividuelle dans la perception qualitative et hédonique des odeurs. Sans aller jusqu'à une explication totalement déterministe selon laquelle la perception olfactive serait « inscrite dans la molécule », les résultats de cette thèse renforcent ainsi l'idée que la perception hédonique et qualitative de l'odeur est construite à travers une hiérarchie de traitements débutant par l'association d'une structure moléculaire bien précise (ou d'un attribut particulier) et d'un ensemble de récepteurs olfactifs. L'expression différentielle de ces récepteurs olfactifs selon les individus et les populations, ainsi que l'apprentissage par simple exposition ou par acquisition d'une expertise, coloreront alors de manière personnelle la valence et la qualité perçue des odeurs, conduisant ainsi à une hétérogénéité interindividuelle en matière de perception olfactive
In a society moving forward and wanting to cut with his animal side, olfactory perception has been judged unnecessary and limited to its simplest expression. Unsurprisingly, olfactory perception was found to be one of the most difficult dimensions to understand in our sensory universe. This dissertation examines the perception of odors in humans. The research effort has been focused on two important aspects of smell: the hedonic valence of odor (ie the pleasantness or unpleasantness of the sample) and odor quality (eg, its floral or fruity note). Olfaction is also known to be highly variable from one individual to another. Indeed, although some odors are perceived in the same way by the majority of the population, many others are perceived very differently between individuals. Thus, the main objective of the research was to provide some explanation on important factors of inter-individual variability in the qualitative and hedonic perception of odors. Without making the complete deterministic claim that olfactory perception is "written in the molecule", the results in this dissertation reinforce the idea that the hedonic and qualitative perceptions of smell are built through a hierarchy of treatments starting with the combination of molecular structure (or of a particular structural attribute) and a very specific set of olfactory receptors. The difference in expression of these olfactory receptors as individuals and populations, as well as learning by mere exposure or acquisition of expertise will then color in a personal way the valence and perceived quality of odors, leading to inter-individual heterogeneity in olfactory perception

La compréhension des mécanismes cérébraux régulant la prise alimentaire est devenue cruciale face à la pandémie mondiale d’obésité. L’ingestion d’aliments est sous le contrôle d’un large réseau de structures cérébrales qui régulent la balance énergétique en régulant l’apport de nourriture et la dépense énergétique. Etant donné l’importance de l’olfaction dans l’appréciation des aliments, il est primordial d’identifier des mécanismes précis liant olfaction et nutrition.Nous avons choisi d’étudier l’activité dans le Bulbe Olfactif principal (BO), la première structure cérébrale qui permet la représentation spatiotemporelle des odeurs. De façon intéressante, des récepteurs aux hormones anorexigènes et orexigènes sont exprimés à la fois dans l’hypothalamus et le BO. Toutefois, l’impact de la leptine (et de l’obésité) sur l’activité du BO in vivo demeure inconnu.Pour évaluer l’action de la leptine et de l’obésité sur la plasticité olfactive, nous avons choisi le modèle murin ob/ob. Nous avons d’abord décrit la répartition spatiale de l’activité dans le BO en réponse à une odeur alimentaire et à une odeur neutre chez ces souris en les comparant à des souris témoins grâce une technique de neuroimagerie fonctionnelle, l’Imagerie par Résonance Magnétique renforcée au Manganèse (MEMRI). Par le développement d’une méthode de comparaison statistique indépendant de l’utilisateur, le SPM (Statistical Parametric Mapping), nous avons mis en évidence une augmentation de l’activité spontanée et de l’activité induite par odeur alimentaire dans le BO des ob/ob. Cependant, l’activité induite par une odeur neutre n’était pas plus élevée. L’injection de leptine a pour résultat d’augmenter le signal MEMRI dans les couches profondes du BO et ne restaure que partiellement l’activité des ob/ob. En quantifiant la neurogenèse dans le BO par injections de BrdU, nous avons mis en évidence une survie accrue des cellules granulaires et périglomerulaires chez les ob/ob.Pour évaluer la dynamique temporelle de l’activité du BO, nous avons enregistré par électrophysiologie les variations de l’activité oscillatoire du potentiel de champ local dans les couches profondes du BO pendant l’apprentissage d’une tâche de discrimination olfactive, le Go/NoGo. L’apparition d’une oscillation lente dite bêta (15-40 Hz) pendant cet apprentissage est un marqueur fonctionnel de l’état du réseau olfactif. Elle est dépendante des retours centrifuges provenant du cortex olfactif, majoritairement du cortex piriforme. Si nous n’avons pas observé de différence importante dans la discrimination olfactive, nous avons en revanche mis en évidence un problème motivationnel chez les animaux ob/ob, qui n’effectuaient la tâche que si la récompense hydrique contenait du sucre. Nos enregistrements montrent une forte augmentation des oscillations bêta chez les souris obèses après apprentissage comparé aux souris témoins
Olfaction makes possible both the detection and the processing of odors related to food location and palatability. Interestingly, receptors to anorexigen and orexigen hormones and neuropeptides found in the hypothalamus are also expressed in the main olfactory bulb (MOB), suggesting that feeding state has an impact on odor representation. However, neuronal mechanisms linking olfaction, food intake and metabolic disorders are still unclear. In this PhD thesis, we wanted to further understand mechanisms of the olfactory-feeding crosstalk and tested the effects of obesity on olfactory activity in the MOB. Leptin, a peptidergic hormone produced by adipocytes, is a major regulator of the energy balance and inhibits food intake. Ob/ob mice are deficient in leptin from birth and are widely used as a murine model of obesity. We used a functional neuroimaging technique, Manganese Enhanced Magnetic Resonance Imaging (MEMRI), in association with statistical parametric mapping (SPM) to monitor food odor-evoked spatial activity in the MOB of these mice. Using MEMRI, we found that odor-evoked signal is different, both in terms of intensity and localization between lean and ob/ob mice for the spontaneous activity and in response to food odor. However, this is not the case for a neutral odor. Moreover, leptin impacts both spontaneous activity and food odor-evoked signal intensity in both groups. Interestingly leptin strongly activates deep layers (mitral cell layer and mainly granule cell layer) of the MOB. To pinpoint what cellular/molecular mechanisms can be responsible for these changes in the spatial distribution of activity, we analyzed the effects of the lack of leptin on the composition and activity of the MOB cellular network.We quantified bulbar adult neurogenesis and found that 21 days after BrdU injections, a cell birth marker, ob/ob mice showed an increased number of both new periglomerular and granular cells as compared to control, suggesting that leptin regulates new neuron elimination. We also tested whether an inflammation could be occurring in the MOB. Using RTPCR of different neuronal and glial markers we did not observe strong signs of inflammation. Then we probed changes in local network activity in the deep layers of the MOB by recording local field potentials during a Go/NoGo odor discrimination task. We observed that the power of beta oscillations, the functional marker of the olfactory network between the MOB and the olfactory cortex, is way higher in the MOB of ob/ob mice compared to control mice

L’olfaction participe à l’élaboration de la valeur hédonique des aliments et à la régulation de la prise alimentaire. Réciproquement, la détection des odeurs alimentaires est influencée par le statut métabolique. Le jeûne augmente les performances olfactives, notamment en augmentant l'activité neuronale dans le bulbe olfactif (BO). Au sein des glomérules du BO, les synapses glutamatergiques entre les neurones sensoriels olfactifs et les cellules mitrales sont régulées par des astrocytes, des neurones périglomérulaires et des afférences centrifuges. En tant que partenaires synaptiques, les astrocytes sont à l’origine de mécanismes de métaplasticité dans le système nerveux central, qui pourrait participer à la régulation métabolique de la réponse olfactive au niveau du BO. Afin de tester si les astrocytes glomérulaires du BO sont impliqués dans la détection du statut métabolique par le système olfactif, nous avons comparé le déploiement des prolongements astrocytaires glomérulaires, par quantification de l’aire occupée par la GFAP chez des rats nourris et mis à jeun.Le déploiement astrocytaire est nettement augmenté chez les rats à jeun par rapport aux rats nourris, dans toutes les régions du BO dès 17h de jeûne. L'administration intra-peritoneale du peptide anorexigène PYY3-36 ou de glucose chez des rats à jeun diminue leur prise alimentaire ou restaure leur glycémie respectivement, et abolit dans les deux cas l'augmentation du déploiement astrocytaire induite par le jeûne. L'application directe des peptides orexigènes ghréline et NPY sur des tranches de BO entraîne une augmentation du déploiement astrocytaire alors que l'application de PYY3-36 entraîne une rétraction astrocytaire au sein des glomérules. Ces résultats concordent avec les variations de la morphologie des astrocytes, observées respectivement en situation de jeûne ou de satiété.Le déploiement des prolongements astrocytaires glomérulaires varie donc en fonction de l'état métabolique des rats, et il est influencé par les peptides régulant la prise alimentaire. Cetteplasticité pourrait participer à l'adaptation de la sensibilité olfactive à l’état métabolique des individus
Olfaction plays a key role in the elaboration of the hedonic value of foods and the regulation of food intake. Reciprocally, the detection of food odors is influenced by the metabolic state. Fasting increases olfactory performances, notably by increasing neuronal activity in the olfactory bulb (OB). Within the OB glomeruli, the glutamatergic synapses between olfactory sensory neurons and mitral cells are regulated by astrocytes, periglomerular neurons and centrifugal afferents. Astrocytes, which support mecanisms of metaplasticity in the brain, may drive the metabolic regulation of the olfactory response in the OB. To test whether OB glomerular astrocytes are involved in the metabolic sensing of the olfactory system, we compared the astroglial processes expansion by quantification of the GFAPlabelled area in fed and fasted rats.Astroglial spreading was markedly increased in fasting rats, as compared to fed rats, in all regions of the OB after 17h-fasting. Intra-peritoneal administration of the anorexigenic peptide PYY3-36 or glucose in 17h-fasted rats respectively decreased their food intake or restored their glycemia and both reversed the increased astroglial deployment induced by fasting. Direct application of orexigenic peptides ghrelin and NPY on OB acute slices, resulted in an increase of the astroglial deployment, whereas application of PYY3-36 oppositely resulted in astroglial retraction within the glomeruli. These results are in close agreement with the effects of fasting or satiation on the morphology of astrocytes.The deployment of the glomerular astroglial processes clearly varies according to the metabolic state of the rats, and is influenced by food intake regulatory peptides. This plasticity may participate in the adaptation of the olfactory sensitivity to food intake

L'etude de la relation olfaction-emotion n'a ete possible qu'avec l'evolution des donnees classiques de la neurophysiologie et des methodes de mesures multiparametriques du systeme nerveux autonome: sna. L'analyse du niveau tonique montre que la relation entre la relaxation et l'aspect agreable des odeurs est forte, excepte pour les odeurs trigeminees. L'analyse du niveau phasique montre que: (1) qu'il n'existe pas de relation preferentielle entre l'olfaction et les emotions ; (2) que chaque odeur est associee a un motif du sna qui peut etre traduit en emotion de base ; (3) que le sna differencie les odeurs agreables des desagreables et parmi les agreables, les trigeminees et celles evocatrices d'experiences desagreables ; (4) que globalement, il existe une relation variable entre la valence hedonique et les parametres sna en reponse a des odeurs. Cette relation est d'autant plus forte qu'on effectue une analyse individuelle et/ou que l'on considere le motif global ; (5) une bonne concordance entre les emotions determinees a partir du sna et celles definies verbalement par les sujets, sauf pour la colere qui semble etre une emotion reprimee ; (6) que la charge emotionnelle liee a l'odeur n'est pas plus forte que celle evoquee par une autre stimulation mais tres liee a la memoire d'une experience desagreable. L'odeur possede donc un fort pouvoir evocateur. En consequence, on peut considerer que les reponses sna sont un bon indicateur de l'inconscient des sujets et que les signes neurovegetatifs des reactions affectives, peuvent sans doute etre considerees comme les temoins du processus cognitif d'analyse globale des odeurs

Ces travaux ont pour but d'étudier des mécanismes centraux de l'olfaction, et la manière dont ils sont intégrés dans les processus de régulationémotionnelle. Les stratégies de distraction et de réévaluation ont fait l'objet de deux expériences distinctes en IRMf, dans lesquelles les sujets devaientdiminuer l'intensité d'émotions suscitées par des odeurs. Dans une troisième expérience, des données psychophysiques et psychophysiologiques ont étécollectées pour évaluer la capacité d'une odeur agréable à réguler un sentiment négatif préalablement induit par uneimage désagréable.Les résultats montrent que la régulation d'émotions induites par des odeurs mobilise des aires cérébrales décrites dans les études utilisant du matérielvisuel (cortex préfrontal, lobule pariétal inférieur, gyrus temporal moyen) mais aussi d'autres plus spécifiques à cette modalité sensorielle (insula, gyrusfusiforme, gyrus lingual). De plus, le cortex préfrontal semble moduler certaines aires du cortex olfactif comme le cortex piriforme et le cortexorbitofrontal lorsque les sujets utilisent une stratégie de distraction. Les données issues de la troisième expérience révèlent également qu'une odeuragréable permet de diminuer l'impact d'un affect négatif préalablement induit, tant au niveau subjectif que psychophysiologique.Par conséquent, il semble exister chez l'Homme une réelle capacité à la régulation des émotions induites par des odeurs. Ce processus met enjeu desrégions habituellement décrites pour la régulation d'émotions induites par des stimuli visuels, mais également d'autres aires plus spécifques.De plus, les odeurs elles-mêmes sont capables de réguler une émotion négative
The research presentee in this thesis aimed to study neural mechanisms of olfaction, and the way they are integrated in emotion regulation processes. Distraction and reappraisal strategies were studied using fMRI in two separate experiments in which subjects had to decrease the intensity of emotions induced by odors. In a third experiment, psychophysical and psychophysiological data were collected to assess the ability of pleasant odors to down-regulate negative feelings induced by unpleasant pictures. The results show that the regulation of odor-triggered emotions recruits brain areas that are usually described in studies based on Visual stimulations (prefrontal cortex, inferior parietal lobule, middle temporal gyrus) but also others more specic to this sensory modality (insular cortex, fusiform gyrus, lingual gyrus). Moreover, the prefrontal cortex seems to modulate the activity within olfactory areas, such as the piriform and the orbitofrontal cortex when subjects use distraction. The data from the third experiment also reveal that a pleasant odor is able to decrease negative aects that have been previously induced by unpleasant pictures, both at subjective and psychophysiological level.Therefore, it appears that odor-triggered emotions can be down-regulated by both distraction and reappraisal strategies. This processinvolves brain regions usually recruited by the regulation of visual-triggered emotions, but also other areas more specic to theregulation of emotions elicited by odors. Moreover, odors themselves can regulate negative feelings

L’objectif de ce travail de thèse était de vérifier l’hypothèse selon laquelle les troubles olfactifs peuvent constituer des marqueurs de la dépression. Tout d’abord, deux études longitudinales ont évalué l’effet du traitement antidépresseur sur les atteintes olfactives et émotionnelles. Deux autres études ont étudié quelles atteintes olfactives peuvent aider à différencier la dépression d’une maladie d’Alzheimer débutante. Les résultats de ce travail ont confirmé la présence de marqueurs olfactifs d’état (pour les aspects hédonique et émotionnel) et de trait (pour les atteintes en rapport avec des capacités cognitives) dans la dépression. Par ailleurs, nos données ont mis en évidence des profils d’altérations différents dans la dépression et la maladie d’Alzheimer débutante, concernanat la mémoire de reconnaissance et l’identification des odeurs, ce qui pourrait aider à différencier ces deux maladies. D’autres travaux devront confirmer l’implication de ces marqueurs dans l’efficacité de la thérapie, le suivi et le diagnostic précoce des patients
The aim of this study was to test the hypothesis of olfactory deficits as potential markers of depression. Firstly, two longitudinal studies have evaluated the effect of antidepressant treatment on olfactory and emotional alterations. In two other studies, we wanted to investigate which olfactory deficits could differentiate depression and early stage of Alzheimer’s disease. The results have confirmed the presence of state (for hedonic and emotional aspects) and trait (for alterations involving cognitive capacities) olfactory markers of depression. Besides, we have demonstrated two different profiles of alterations in depression and early stage of Alzheimer’s disease, concerning odors’ memory recognition and identification, which could help to discriminate these two diseases. Other investigations are necessary to confirm the implication of these markers in the efficiency of the therapy, the diagnostic and the take care of patients

Infochemical communication is ubiquitous amongst all living organisms, and particularly important in insects. Because smell being the most common basic means of chemical communication, infochemical blends must be constantly decoded in order to proclaim their readiness to mate, to mark out territorial boundaries, to warn off intruders and predators or, in some cases, to locate food or predators with millisecond precision. The central challenge of the thesis was to mimic nature in both cellular and molecular levels on to a technological platform that aids in the development of a new class of technology employing chemicals alone to communicate over space and time. This thesis describes a body of work conducted in the development of a miniaturised, smart and label-free cell-based chemoreceiver for artificial insect olfaction, as part of the development of a novel biomimetic infochemical communication system. A surface acoustic wave based microsensor has been utilized to engineer and develop a chemoreceiver system that mimics the cellular and molecular mechanisms occurring during infochemical detection and decoding in insects. Successful recovery of ratiometric information with the aid of polymer-based gas-phase measurements, established the concept of chemical communication. Thus, small scale, high-throughput infochemical communication has been realized by a combination of precise spatiotemporal signal generation using fruit volatiles and insect sex pheromones with highly sensitive detection and signal processing. This was followed by the investigation of the feasibility of using the prototype cell-based biosensor system in a static mode for artificial insect olfaction applications, mimicking the cellular detection in the receptor/antenna apparatus of insects. Finally, as part of the development of a compact and low-power portable chemoreceiver system, the discrete sensor drive and interface circuitry was deployed in an analogue VLSI chip, thereby overcoming the associated measurement complexity and equipment cost, in addition to extending the reach and functionality of point of use technologies.

Senegalese sole is a flatfish species with increasing importance for the aquaculture industry due to its good performance (survival and growth) in captivity and high market price.However,one of the principal bottlenecks to the expansion of the species culture is the reproductive behavioural dysfunction in cultured males,which complicates establishing a closed cycle in captivity.The reproductive behavioural dysfunction is exhibited by the cultured males that do not participate in the courtship.Therefore, Senegalese sole production relies on wild males,which is unsustainable in the long term.With the aim to understand and look for solutions to this bottleneck,the present thesis focuses on different aspects of behaviour related to reproduction and the olfactory system. The effect of the presence of spawning wild Senegalese sole breeders on the reproductive behaviour and reproductive success of cohabiting cultured breeders was examined.Three groups were established,1 formed by cultures sole and 2 mixed groups (cultured and wild).Fertilised spawns were not obtained from the control group.However,fertilised spawns were obtained from the mixed-origin groups.Cultured males were observed to participate increasingly in the courtship and one cultured male fertilised 2 spawns.These results suggested a learning process in this species for behaviours associated to reproduction.With the olfactory analysis,the structure of the olfactory rosettes of 2 groups from different origin of Senegalese sole juveniles were compared.No significant differences in tissue structure,cell types and cellular distribution pattern were observed between origin specimens,however,differences were found between rosettes in number of lamellae and amount of goblet cells in the ridge region of the lamella,which were more frequent in the lower rosette.Related to the comparison of transcriptomic profiles (RNA-seq) of the upper rosette in cultured and wild sole mature males,the difference in transcripts of some olfactory receptors and other transcripts associated with the control of reproduction demonstrated clear differences in functionalities between origins.Related to the olfactory sensitivity of cultured sole, juveniles and adults to urine from mature conspecific (wild and cultured) was evaluated using EOG.Urine was confirmed to be a potent olfactory stimulus for juvenile and adult.In addition to this, urine from mature females evoked a small, but significant increase in plasmas levels of LH in mature males,further demonstrating that urine play a role in reproduction in this species.Related to dominance in Senegalese sole juveniles were used to conduct 2 dyadic tests (feeding response and territory) and group tests.This was the first study related to dominance behaviour in this species, which could be very relevant to the low participation in the parental contribution during the spawning season.Three parameters related to feeding response, 2 variables related to territory and 2 index in the group test were extracted to differentiate between dominant and subordinate sole.Moreover,2transcripts related to neurogenesis and neuroplasticity were differentially expressed between dominant and subordinate.In the present study three stress coping styles categories were found (proactive,intermediate and reactive) in Senegalese sole juveniles.Moreover,there were four transcripts related to metabolism and feeding behaviour which linked behavioural stress coping categories with brain gene expression.All together these advances strengthen the importance of these research lines as areas that can give a solution to the reproductive dysfunction that can enable the aquaculture industry to close the species life cycle in captivity to make sole culture sustainable.
El lenguado Senegalés es una especie de pez plano que está en constante crecimiento de producción dentro de la industria de la acuicultura debido a su buena capacidad de supervivencia y crecimiento en cautividad,además de poseer un elevado precio en el mercado.En cambio,uno de los principales problemas de expansión del cultivo del lenguado es la disfunción reproductiva asociada al comportamiento complicando el cierre del ciclo de vida de esta especie en cautividad.La disfunción reproductiva se ve en los machos de cultivo que no participan en el cortejo.Consecuentemente,la producción del lenguado recae en los machos salvajes siendo insostenible a largo plazo.Esta tesis tiene como objetivo principal entender y buscar posibles soluciones a este problema enfocándose en diferentes aspectos relacionados con la reproducción y el sistema olfativo.Primero se realizó un análisis de efecto de la presencia de lenguados salvajes que se reproducen,en el cortejo y el éxito reproductivo de los lenguados de cultivo,que no se reproducen.Se formaron 3 grupos,1 de cultivo (control) y 2 mezcla (cultivo y salvajes).No se obtuvo puestas fecundadas del grupo control,en cabio si se obtuvo de los grupos mezcla,viendose por primera vez un aumento de participación de los machos de cultivo,donde un macho de cultivo fertilizó 2 puestas.Estos resultados sugieren un posible proceso de aprendizaje del cortejo por parte de los machos de cultivo.Con el análisis del olfato,primero se realizó una descripción y comparación histológica de la estructura de ambas rosetas olfativas de dos grupos de lenguados juveniles (cultivo y salvaje).No se hallaron diferencias significativas en la estructura tisular, tipos de células y distribución celular entre lenguados de diferente origen, en cambio, se encontraron diferencias entre las rosetas en número total de lamelas y en cantidad de células goblet concentradas en la parte apical de las lamelas siendo más frecuente en la roseta inferior.Con referencia a la comparación transcriptómica (RNA-seq) de la roseta superior en machos maduros salvajes y de cultivo,hubo diferencias significativas en transcritos asociados a receptores olfativos y de reproducción mostrando claras diferencias en la funcionalidad de la roseta en lenguados de diferente origen.En referencia a la sensibilidad olfativa a la orina del lenguados maduros medida a través del EOG,se demostró que la orina es un potente estimulante olfativo en lenguados juveniles y adultos de cultivo y además el incremento de LH en plasma de los machos adultos utilizados en este estudio demostró que la orina juega un papel importante en la reproducción de dicha especie.En referencia a los estudios de dominancia en lenguados juveniles,se utilizaron 2 pruebas diádicas(alimentación y territorio) y una grupal extrajeron 3 parámetros de dominancia asociados a la alimentación,2 variables asociadas al territorio y 2 índices en el test grupal los cuales diferenciaron entre dominantes y subordinados.Además hubo dos transcritos relacionados con la neurogenesis y la neuroplasticidad que se expresaron diferencialmente entre dominantes y subordinados.Este estudio ha sido el primero en reportar la dominancia como comportamiento en esta especie, la cual podría ser relevante debido a la baja contribución parental durante la época de puesta.Así mismo,se determinaron 3 categorias de estilos de afrontamiento al estrés (proactivos,intermedios y reactivos) en lenguados juveniles.Se encontraron 4 transcritos asociados al metabolismo y comportamiento de alimentación que relacionó los prfiles de comportamiento con la expresión génica cerebral en lenguados juveniles siendo genes importantes a nivel biolígico y funcional. Conjuntamente estos avances fortalecen la importancia de estas líneas de investigación como áreas que pueden dar solución a la disfunción reproductiva pudiendo cerrar el ciclo de vida del lenguado en cautividad para hacer el cultivo sost
El llenguado Senegalès es una espècie de peix pla que està en constant creixement de producció dins de la industria de l'aqüicultura degut a la seua capacitat de supervivència i creixement en captivitat,a més de posseir un elevat preu al mercat.En canvi,un dels principals problemes d'expansió del cultiu d'aquesta espècie és la disfunció reproductiva associada al comportament que complica tancar el cicle de vida del llenguado en captivitat.La disfunció reproductiva s'observa als mascles de cultiu que no participen al seguici.Conseqüentment,la producció del llenguado Senegalès depèn dels mascles salvatges el qual es insostenible a llarg termini.Esta tesi té com objectiu principal entendre i buscar possibles solucions a aquest problema enfocant-se en diferents aspectes relacionats amb la reproducció i el sistema olfactiu.Primer es realitzà un anàlisi d'efecte de la presència de llenguados salvatges que es reprodueixen en el seguici i l'èxit reproductiu dels llenguados de cultiu que no es reprodueixen.Es formà 3 grups,un de cultiu (control) i 2 mescla (cultiu i salvatges).No s'obtingué posts fecundades del grup control,en canvi si s'obtingueren dels grups mescla,veient un augment de participació dels mascles de cultiu per primera volta,on un mascle de cultiu va fertilitzar 2 postes.Aquests resultats suggereixen un procés d'aprenentatge del seguici per part dels mascles de cultiu.Amb l'anàlisi de l'olfacte,primer es realitzà una descripció i comparació estructural histològica de ambdues rosetes olfactives de 2 grups de llenguados juvenils dels dos orígens.No es trobà diferències en l'estructura tissular,tipus de cèl·lules i distribució entre llenguados de diferent origen,en canvi,es trobà diferències entre rosetes en nombre total de lamel·les i quantitat de cèl·lules goblet concentrades a la part apical de la lamel·la més freqüents a la roseta inferior.En referència a la comparació transcriptómica (RNA-seq) de la roseta superior en mascles madurs salvatges i de cultiu,es trobà diferències en transcrits associats a receptors olfactius i de reproducció mostrant clares diferències en la funcionalitat de la roseta en llenguados de diferent origen.En referència a la sensibilitat olfactiva de l'orina de llenguados madurs mesurada amb EOG,es demostrà que l'orina es un potent estimulant olfactiu en llenguados juvenils i adults de cultiu i l'increment de LH en sang dels mascles adults utilitzats en aquest estudi demostrà que l'orina juga un paper important en la reproducció d'aquesta espècie.En referència als estudis de dominància de llenguados juvenils utilitzant 2 probes diàdiques (alimentació i territori) i 1 grupal,van extraure 3 paràmetres de dominància associats a l'alimentació,2 variables associades amb el territori i 2 índex en el test grupal els quals diferencià entre dominants i subordinats.Aquest etudi ha sigut el primer en reportar la dominància com a comportament en aquesta espècie,la qual podria ser important degut a la baixa participació parental durant l'època de posta.Així mateix,es determinà 3 categories d'estil d'afrontament a l'estrès (proactius,entremitjos i reactius) en llenguados juvenils.Es van trobar 4 transcrits associats al metabolisme i comportament d'alimentació sent tots ells gens d'importància biològica i funcional que s'expressaren diferencialment entre perfils de comportament.Conjuntament aquests avanços enforteixen la importància d'aquestes línies d'investigació com àrees que puguin donar solució a la disfunció reproductiva podent tancar el cicle de vida del llenguado en captivitat per a fer la producció d'aquesta espècie sostenible en l'industria de l'aqüicultura.
Fatsini Fernández, E. (2017). Reproduction, olfaction and dominance behaviour in Senegalese sole (Solea senegalensis) [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/81550
TESIS

Les comportements olfactifs nécessitent de reconnaitre les odeurs sur une large gamme de concentration tout en restant sensible aux changements de concentration. Pour accomplir cette tâche paradoxale, le système olfactif doit façonner des représentations des odeurs qui soient à la fois dépendantes et indépendantes de leurs concentrations.Nous avons combiné des techniques de génétique murine, microscopie biphotonique, et enregistrements neurophysiologiques extracellulaires pour caractériser l’activité neuronale en réponse aux odeurs dans le bulbe olfactif et le cortex olfactif (piriforme) de la souris. En utilisant une souris au « nez monoclonal », nous montrons que les circuits du bulbe olfactif sont capables d’amplifier les entrées sensorielles très faibles, et d’atténuer les entrées envahissantes. En revanche, nous observons que le niveau d’activité neuronale induite par les odeurs dans le cortex piriforme est globalement indépendant de leurs concentrations. En outre, nous avons identifié une sous-population de neurones du cortex piriforme encodant l’identité d’une odeur indépendamment de sa concentration. Nos résultats d’imagerie calcique in vivo et d’enregistrement neurophysiologiques suggèrent que cette invariance à la concentration dans le cortex piriforme est assurée par les interneurones positifs à la paravalbumine, une sous-population de neurones inhibiteurs.Ces résultats mettent en évidence deux étapes différenciées du traitement de l’information dans les voies neurales de l’olfaction : tandis que le bulbe olfactif normalise les entrées sensorielles, les microcircuits du cortex piriforme intègrent cette information en composantes sensorielles distinctes
Olfactory behaviors require the identification of odors across a large range of different concentrations, yet are exquisitely sensitive to changes in odor concentrations. To accomplish this seemingly paradoxical task the olfactory system must generate odor representations that are, at once, both concentration-dependent and concentration-invariant.We have used a combination of mouse genetics, in vivo two-photon microscopy, and extracellular multielectrode recording techniques to characterize odor-evoked activity in the olfactory bulb and olfactory (piriform) cortex of mice. Taking advantage of a mouse with a “monoclonal nose” in which the sensory input map is strongly perturbed, we show that olfactory bulb circuits are able to amplify very weak sensory inputs, and to suppress pervasive input.In contrast, we found that the overall level of odor-evoked neural activity in the piriform cortex is largely concentration-invariant. Moreover, we identified a small subpopulation of odor-responsive piriform neurons, which encodes odor identity independent of concentration. In vivo calcium imaging and extracellular multielectrode recordings suggest that parvalbumin-expressing interneurons, a subpopulation of inhibitory neurons, mediate concentration invariance in the piriform cortex.These results highlight contrasting processing mechanisms of sensory information along the olfactory pathway: while the olfactory bulb normalizes sensory inputs, microcircuits of the piriform cortex integrate this information into distinct sensory features. This process may allow for the simultaneous representation of identity and intensity in the olfactory system

Comment les souvenirs olfactifs sont-ils stockés dans notre cerveau? Plusieurs études suggèrent que le cortex olfactif (piriforme) jouerait un rôle important dans la mémoire olfactive. J'ai donc voulu déterminer si cette région du cerveau est impliquée dans le rappel d'un souvenir olfactif. Pour cela, j'ai manipulé l'activité des neurones du cortex piriforme ayant été actifs pendant un apprentissage olfactif aversif, en utilisant cfos comme marqueur d'activation neuronale. Plus précisément, j'ai choisi de travailler avec la lignée de souris transgénique cfos-tTA (et de manière moins développée avec la lignée fosCreERT2) et d'utiliser les récepteurs "DREADDs". J'ai montré que lors du test de mémoire, l'inactivation des neurones du cortex piriforme actifs pendant l'apprentissage rend la souris amnésique. De manière réciproque, la réactivation artificielle de ces neurones récupère le souvenir de l'association odeur-stimulus aversif. Ainsi, une trace mnésique se forme au niveau du cortex piriforme, et plus précisément au niveau des neurones actifs lors de l'apprentissage. Ce résultat ouvre la voie à de nombreux champ d'investigations pour mieux comprendre les mécanismes de la mémoire. J'ai choisi d'explorer de manière préliminaire l'effet de l'apprentissage sur la représentation des odeurs au niveau du cortex piriforme. En parallèle, en utilisant une approche théorique, j'ai étudié si un modèle basé sur les variations de potentiel de membrane dendritique pouvait prédire l'occurrence d'un type de plasticité à une synapse corticale. L'ensemble de ces travaux ont permis d'accroître nos connaissances sur le fonctionnement de la mémoire olfactive
Olfaction is an evolutionarily old sensory modality that plays key roles in the survival of many species and is densely interwoven with memory and emotions. However, how odor memories are formed and stored in the brain remains largely unknown. To address these questions, we studied the olfactory (piriform) cortex of mice, which is a good candidate for encoding olfactory memory traces. We used c-fos as a marker of neural activity and the cfos-tTA transgenic mouse line (and the fosCreERT2 mouse line to a lesser extent) to selectively express chemogenetic receptors (DREADDs) in piriform neurons that are active during an olfactory fear conditioning task. We found that chemogenetically reactivating these ensembles artificially retrieves the memory while chemogenetically silencing them impairs memory retrieval. Piriform neurons active during olfactory learning thus play a key role in memory retrieval. These results open new horizons in understanding memory trace formation. We decided to explore in a preliminary way how learning shapes piriform network properties. In parallel, using a theoretical framework, we investigated if a model based on dendritic voltage could predict synaptic plasticity. Taken together, these experiments will provide important insights into the mechanisms of odor coding and memory

L'olfaction est un sens clé dans l'adaptation du comportement. Pour permettre des actions appropriées le système olfactif doit effectuer des discriminations fines entre stimuli. Les performances de discrimination peuvent être améliorées via l'apprentissage perceptif et une structure cérébrale clé : le bulbe olfactif. Cette structure est cible d'une forme de plasticité particulière qui est la neurogenèse adulte. C'est là que des nouveaux neurones, majoritairement des cellules granulaires, régulent l'activité des cellules relais. Il a été montré que ces neurones sont requis pour un apprentissage perceptif.La question centrale de cette thèse est d'élucider le rôle et la spécificité des nouveaux neurones dans l'apprentissage olfactif complexe et changeant.Nous avons d'abord étudié l'effet d'un apprentissage perceptif complexe sur la neurogenèse adulte. Cette étude à démontré la nécessité et suffisance des nouveaux neurones dans l'apprentissage perceptif simple. Elle a aussi montré que lorsque l'apprentissage devient complexe, un réseau plus large est recruté, requérant les neurones préexistant.L'environnement olfactif est aussi changeant. Dans une seconde étude nous avons investigué comment la mémoire olfactive est altérée par nouvelle mémoire et le rôle de la neurogenèse adulte dans ce processus. Elle a montré le rôle des nouveaux neurones à sous tendre la mémoire olfactive et l'importance du délai entre apprentissages dans la stabilisation mnésique.Finalement, le recours aux neurosciences computationnelles a eu pour but de définir le rôle des nouveaux neurones granulaire au niveau du premier niveau de transformation de l'information et comment le raffinement des représentations sensorielles émerge par décorrelation.Pour conclure, la perception olfactive est changeante en fonction des modifications environnementales et cette plasticité est sous tendu par une plasticité du circuit du bulbe olfactif, due en grande partie à la neurogenèse adulte
Olfaction is a key player in behavioral adaptation. To perform tasks accurately, the olfactory system has to perform fine discrimination between very close stimuli. The discrimination performances can be enhanced through perceptual learning and a key cerebral structure in this is the olfactory bulb. This structure is the target of a specific form of plasticity that is adult neurogenesis. In this structure, adult-born neurons differentiate mostly in granule cells that regulate the activity of the relay cells. It has previously been shown that these neurons are required to perform perceptual learning. The central question of this thesis work is to elucidate both the role and the specificity of adult born neurons during complex or changing olfactory learning.We first studied the effect of complex perceptual learning on adult neurogenesis. This study demonstrated the necessity and sufficiency of adult-born neurons for simple olfactory learning. It also showed that when learning becomes complex, a larger neural network is involved requiring preexisting neurons.The olfactory environment is also changing. In a second study we investigated how the memory of an olfactory information is altered by the acquisition of a new one and what is the role of adult neurogenesis in this process. This second study highlighted the role of adult-born neurons in underlying olfactory memory and the importance of delay between learning for memory stabilization.Lastly, an approach relying on computational neurosciences aimed at outlining a computational framework explaining the role of adult-born granule cells in early olfactory transformations and how sharpened sensory representations emerge from decorrelation.To conclude, olfactory perception is changing according to environmental modifications and this plasticity is underlain by an important plasticity of the olfactory bulb circuitry due in large part to adult neurogenesis

La création d'un parfum procède d'une démarche artisanale: un créateur, le parfumeur, compose "un jus” en utilisant un nombre plus ou moins grand de matières premières naturelles ou synthétiques. Il s'agit d'une démarche artisanale en ce sens que le parfumeur utilise son savoir-faire et son goût personnel pour créer une oeuvre originale. Mais le parfum est aussi un produit destiné à la consommation, qui doit plaire et être vendu au plus grand nombre. Il est donc nécessaire pour les parfumeurs de disposer d'un outil de communication avec les consommateurs, afin de créer un jus le plus proche possible "des tendances du marché". Le dialogue entre parfumeurs et consommateurs est généralement assuré par les services marketing des sociétés productrices de parfums. Mais l'absence d'une véritable méthode d'analyse descriptive des odeurs conduit ces services à qualifier la cible d'un parfum, et non le parfum lui même. Il apparaît donc nécessaire de concevoir une méthode d'analyse descriptive des odeurs permettant un dialogue efficace entre les différents acteurs d'une entreprise de parfumerie. Notre démarche est à placer dans le cadre de ce besoin. Nous avons conduit nos travaux dans le cadre d'un contrat CIFRE, au sein du laboratoire d'analyse sensorielle de la société Bourjois. Cette société a été parmi les premières, dans son domaine, à développer l'analyse sensorielle comme outil de recherche sur la perception des parfums
The creation of a perfume is an artisanal process: a creator. The perfumer, composes "a juice" using a greater or lesser number of natural or synthetic natural or synthetic raw materials. The process is in the sense that the perfumer uses his or her know-how and personal taste to create an original work of art. But perfume is also a product intended for consumption, which must please and be sold to the greatest number. It is therefore necessary for perfumers to have a tool for communicating with communication with consumers, in order to create a juice as close as possible to market trends". Dialogue between perfumers and consumers is generally ensured by the marketing departments of perfume companies. But the absence lack of any real method of descriptive odor analysis leads these departments to not the fragrance itself. It therefore appears necessary to devise a method for descriptive odor analysis to enable effective dialogue between the various players in a perfume company. Our approach is in line with this need. We carried out our work as part of a CIFRE contract, within the sensory analysis laboratory of the Bourjois company. This company was one of the first companies in its field to develop sensory analysis as a tool for research into fragrance perception

1.1-Bulbectomy experiments We focused on how the rat uses olfactory cues in a single-pellet reaching task, which is composed of three sequential learned responses: Orient, Transport and Withdrawal. High-speed video-recording enabled us to describe the features of responses in controls vs. 3–5 and 12–14 days after bilateral bulbectomy in trials with (P trial) vs. without (no-P trial) pellet. In controls: a- the sequence of responses was complete in P trials, while it was interrupted after Orient in no P-trials; b- there is no difference in duration between the first two events of orient in P vs. no-P trials. After bulbectomy: a- the frequency of approach to the front wall decreased; b- the sequence of responses was complete in both P and no-P trials; c- there is an increase in Orient duration due solely to the increased time in slot localisation; d- the first nose contact with the front wall took place below the shelf/pellet level; e- the number of nose touches preceding poking was significantly higher. Otherwise, after Bulbectomy the pattern of reach and the ability to grasp the pellet do not change, suggesting that the preserved whisker/nose tactile input triggers the transport movement. In conclusion, bulbectomy, but not necessarily olfaction, affects Orienting whereas olfaction is used to navigate the box and determines the choice to reach/grasp the target. 1.2 - Bilateral Macrovibrissae trimming and Infraorbital nerve severing experiments Skilled reaching is a complex movement, in which a forelimb is extended to grasp food that is placed in the mouth for eating. In rat, olfaction is used to guide reaching, but the relevance of whisker sense suggests that this could also have a role. To test this hypothesis, we studied skilled reaching behaviour in rats trained in a single-pellet reaching task before and after infraorbital nerve (ION) severing. Bilaterally ION severed rats display an impressive change in the architecture of skilled behaviour already detectable in the first post-surgical recording session. Specifically, the behavioural sequence was interrupted either before approaching the front wall of the box or before poking with the nose into the slot to locate the food pellet. In the following days, rats began to display a new phase of exploration of the front wall with repetitive forelimb movements, a prelude to the reappearance of reaching, which took place between 6 and 12 days after ION severing, depending on the rat. From this time onward the skilled behaviour architecture completely recovered. These findings strongly indicate that whisker sense play a role in guiding skilled reaching behaviour in the rat. 1.3- Skilled Reaching Kinematics experiments In rats, skilled reaching includes orienting (OR), reaching (RC), grasping (GR) and retracting (RT) movements. Here we present the first quantitative description of this behaviour by means of a 3D recording system. OR movement featured three steps: head approaching the front wall (HA), slot localization with head movements (SL), and nose poke through it (PK). SL was the longest-lasting step (p=0.0000), while HA was the fastest (p=0.0000). RC showed two bimodal start point distributions: i) along the X axis, beyond or within the first quartile from the target, long and short RC trajectories were distinguished, each presenting different shapes and velocity peaks; ii) along the Z axis, there were two modalities of reach start, in the stance or swing phase of the last step. 3D plots evidenced that at the end of RC, the wrist/paw occupied the same spatial position as the nose at the end of OR. In GR, averaging the trajectories confirmed the lowering and approach of the marker towards the target. Averaging the velocity profile showed equal amplitude velocity peaks, at around 20–30% of the normalized GR duration, on the X and Z axes. Finally, logistic regression analysis suggested which kinematic variables were decisive for successful prehension.
1.1-Bulbectomy experiments We focused on how the rat uses olfactory cues in a single-pellet reaching task, which is composed of three sequential learned responses: Orient, Transport and Withdrawal. High-speed video-recording enabled us to describe the features of responses in controls vs. 3–5 and 12–14 days after bilateral bulbectomy in trials with (P trial) vs. without (no-P trial) pellet. In controls: a- the sequence of responses was complete in P trials, while it was interrupted after Orient in no P-trials; b- there is no difference in duration between the first two events of orient in P vs. no-P trials. After bulbectomy: a- the frequency of approach to the front wall decreased; b- the sequence of responses was complete in both P and no-P trials; c- there is an increase in Orient duration due solely to the increased time in slot localisation; d- the first nose contact with the front wall took place below the shelf/pellet level; e- the number of nose touches preceding poking was significantly higher. Otherwise, after Bulbectomy the pattern of reach and the ability to grasp the pellet do not change, suggesting that the preserved whisker/nose tactile input triggers the transport movement. In conclusion, bulbectomy, but not necessarily olfaction, affects Orienting whereas olfaction is used to navigate the box and determines the choice to reach/grasp the target. 1.2 - Bilateral Macrovibrissae trimming and Infraorbital nerve severing experiments Skilled reaching is a complex movement, in which a forelimb is extended to grasp food that is placed in the mouth for eating. In rat, olfaction is used to guide reaching, but the relevance of whisker sense suggests that this could also have a role. To test this hypothesis, we studied skilled reaching behaviour in rats trained in a single-pellet reaching task before and after infraorbital nerve (ION) severing. Bilaterally ION severed rats display an impressive change in the architecture of skilled behaviour already detectable in the first post-surgical recording session. Specifically, the behavioural sequence was interrupted either before approaching the front wall of the box or before poking with the nose into the slot to locate the food pellet. In the following days, rats began to display a new phase of exploration of the front wall with repetitive forelimb movements, a prelude to the reappearance of reaching, which took place between 6 and 12 days after ION severing, depending on the rat. From this time onward the skilled behaviour architecture completely recovered. These findings strongly indicate that whisker sense play a role in guiding skilled reaching behaviour in the rat. 1.3- Skilled Reaching Kinematics experiments In rats, skilled reaching includes orienting (OR), reaching (RC), grasping (GR) and retracting (RT) movements. Here we present the first quantitative description of this behaviour by means of a 3D recording system. OR movement featured three steps: head approaching the front wall (HA), slot localization with head movements (SL), and nose poke through it (PK). SL was the longest-lasting step (p=0.0000), while HA was the fastest (p=0.0000). RC showed two bimodal start point distributions: i) along the X axis, beyond or within the first quartile from the target, long and short RC trajectories were distinguished, each presenting different shapes and velocity peaks; ii) along the Z axis, there were two modalities of reach start, in the stance or swing phase of the last step. 3D plots evidenced that at the end of RC, the wrist/paw occupied the same spatial position as the nose at the end of OR. In GR, averaging the trajectories confirmed the lowering and approach of the marker towards the target. Averaging the velocity profile showed equal amplitude velocity peaks, at around 20–30% of the normalized GR duration, on the X and Z axes. Finally, logistic regression analysis suggested which kinematic variables were decisive for successful prehension.

Electronic noses combine an array of cross-selective gas sensors with a pattern recognition engine to identify odors. Pattern recognition of multivariate gas sensor response is usually performed using existing statistical and chemometric techniques. An alternative solution involves developing novel algorithms inspired by information processing in the biological olfactory system. The objective of this dissertation is to develop a neuromorphic architecture for pattern recognition for a chemosensor array inspired by key signal processing mechanisms in the olfactory system. Our approach can be summarized as follows. First, a high-dimensional odor signal is generated from a chemical sensor array. Three approaches have been proposed to generate this combinatorial and high dimensional odor signal: temperature-modulation of a metal-oxide chemoresistor, a large population of optical microbead sensors, and infrared spectroscopy. The resulting high-dimensional odor signals are subject to dimensionality reduction using a self-organizing model of chemotopic convergence. This convergence transforms the initial combinatorial high-dimensional code into an organized spatial pattern (i.e., an odor image), which decouples odor identity from intensity. Two lateral inhibitory circuits subsequently process the highly overlapping odor images obtained after convergence. The first shunting lateral inhibition circuits perform gain control enabling identification of the odorant across a wide range of concentration. This shunting lateral inhibition is followed by an additive lateral inhibition circuit with center-surround connections. These circuits improve contrast between odor images leading to more sparse and orthogonal patterns than the one available at the input. The sharpened odor image is stored in a neurodynamic model of a cortex. Finally, anti-Hebbian/ Hebbian inhibitory feedback from the cortical circuits to the contrast enhancement circuits performs mixture segmentation and weaker odor/background suppression, respectively. We validate the models using experimental datasets and show our results are consistent with recent neurobiological findings.

This thesis addresses key issues of scientific realism in the philosophy of biology and chemistry through investigation of an underexplored research domain: olfaction theory, or the science of smell. It also provides the first systematic overview of the development of olfactory practices and research into the molecular basis of odours across the 19th and 20th century. Historical and contemporary explanations and modelling techniques for understanding the material basis of odours are analysed with a specific focus on the entrenchment of technological process, research tradition and the definitions of materiality for understanding scientific advancement. The thesis seeks to make sense of the explanatory and problem solving strategies, different ways of reasoning and the construction of facts by drawing attention to the role and application of scientific representations in olfactory practices. Scientific representations such as models, classifications, maps, diagrams, lists etc. serve a variety of purposes that range from the stipulation of relevant properties and correlations of the research materials and the systematic formation of research questions, to the design of experiments that explore or test particular hypotheses. By examining a variety of modelling strategies in olfactory research, I elaborate on how I understand the relation between representations and the world and why this relation requires a pluralist perspective on scientific models, methods and practices. Through this work I will show how a plurality of representations does not pose a problem for realism about scientific entities and their theoretical contexts but, on the contrary, that this plurality serves as the most reliable grounding for a realistic interpretation of scientific representations of the world and the entities it contains. The thesis concludes that scientific judgement has to be understood through its disciplinary trajectory, and that scientific pluralism is a direct consequence of the historicity of scientific development.