The honeybee is one of the model species in insect olfaction and its sense of smell is well studied. However, knowledge about the spectrum of odorants detectable to honeybees is limited. One class of odorants that has never been tested so far are the amino acids, which are important constituents of floral nectar. The experiments reported here were conducted in order to (1) determine if the odor of amino acids is detectable to honeybees (Apis mellifera), and (2) determine olfactory detection thresholds in honeybees for detectable amino acid odors. To this end, the proboscis extension reflex, a classical conditioning paradigm that takes advantage of the honeybee’s ability to build a robust association between an odor stimulus and a nectar reward, was used. The results demonstrate that five out of 20 amino acids presented at 100 mM were detectable. The honeybees’ median olfactory detection thresholds for these five amino acids are 12 mM for L-tyrosine and L-cysteine, 50 mM for L-asparagine and L-tryptophan, and 100 mM for L-proline. These threshold values are high in comparison to naturally occurring concentrations in floral nectar, and compared to threshold values obtained in vertebrate species. One possible explanation for these findings is that the size of the olfactory receptor repertoire of honeybees limits their olfactory capabilities in terms of detectability and sensitivity for the odor of amino acids

The olfactory sensitivity of five male CD-1 mice (Mus musculus) for six amino acids was determined using an operant conditioning paradigm. All animals significantly distinguished dilutions as low as 0.01 mM L-cysteine, 3.3 mM L-methionine, 10 mM L-proline, 0.03 mM D-cysteine, 0.3 mM D-methionine and 10 mM D-proline from the odorless solvent, with individual animals displaying even lower detection thresholds. Among the three different L-forms of the amino acids the mice were most sensitive for cysteine and least sensitive for proline, and among the three D-forms the animals displayed a lower sensitivity for D-proline compared to D-cysteine and D-methionine. A comparison between the present data and results obtained with other species showed that the CD-1 mice displayed a higher sensitivity than human subjects and spider monkeys with three (L-Cysteine, D-cysteine and L-proline) of the six amino acids. Results from this report support the idea that the number of functional olfactory receptor genes is not suitable to predict a species’ olfactory sensitivity.

It has been proposed that the various 14-3-3 isotypes and isoforms present in all eukaryotes are largely functionally equivalent. However, this is not consistent with the conservation of multiple isoforms and isotypes, especially in vertebrates with seven 14-3-3 encoding genes and nine isotypes. The hypothesis tested in this thesis is that both isoform-specific and overlapping functions are likely mediated through tissue specific expression, colocalization and dimerization of 14-3-3 proteins occur in vivo. Drosophila melanogaster was selected because it offers a simple, but representative system to study these proteins functionally. This thesis focuses primarily on D14-3-3?, although the expression pattern and phenotypes associated with all three Drosophila 14-3-3s were determined. I first determined the expression pattern of the three different 14-3-3 isotypes (leoI, leoII and D14-3-3?) and described developmental phenotypes associated with mutations in 14-3-3 isotypes in Drosophila. I found that there is partial redundancy with respect to lethality. Both LEO and D14-3-3? appear required for normal germ-line and somatic gonadal development. However, they do not appear to be functionally equivalent with respect to this phenotype since LEO is unable to compensate for the loss of D14-3-3?. I also determined that D14-3-3? mutants have unique phenotypes including deficits in adult cross-vein formation and rapid habituation to olfactory and footshock stimuli. To further understand the unique role that D14-3-3? plays in the adult CNS, I mapped the areas in the brain involved in olfactory and footshock habituation. I found that although the mushroom bodies (MBs) are necessary to inhibit premature habituation such as that exhibited by D14-3-3? mutants, D14-3-3? expression specifically in the MBs is not sufficient to rescue premature habituation. Although the loss of either LEO or D14-3-3? appears to cause a deficit in olfactory associative learning, premature habituation is the cause of the deficit seen in D14-3-3? mutants. As leo mutants do not exhibit a premature habituation phenotype, it appears that within the MBs LEO and D14-3-3? are not functionally equivalent. Therefore, the data supports the hypothesis that 14-3-3s have functional specificity and redundancy likely to represent use of homo and heterodimers in different processes within the tissues of an organism.

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.

<p>The olfactory system is believed to be the oldest sensory system. It developed to detect and analyse chemical information in the form of odours, and its organisation follows the same principles in almost all living animals - insects as well as mammals. Likely, the similarities are due to parallel evolution - the same type of organisation has arisen more than once. Therefore, the olfactory system is often assumed to be close to optimally designed for its tasks. Paradoxically, the workings of the olfactory system are not yet well known, although several milestone discoveries have been made during the last decades. The most well-known is probably the disovery of the olfactory receptor gene family, announced in 1991 by Linda Buck and Richard Axel. For this and subsequent work, they were awarded a Nobel Prize Award in 2004. This achievement has been of immense value for both experimentalists and theorists, and forms the basis of the current understanding of olfaction. The olfactory system has long been a focus for scientific interest, both experimental and theoretical. Ever since the field of computational neuroscience was founded, the functions of the olfactory system have been investigated through computational modelling. In this thesis, I present the basis of a biologically realistic model of the olfactory system. Our goal is to be able to represent the whole olfactory system. We are not there yet, but we have some of the necessary building blocks; a model of the input from the olfactory receptor neuron population and a model of the olfactory bulb. Taking into account the reported variability of geometrical, electrical and receptor-dependent neuronal characteristics, we have been able to model the frequency response of a population of olfactory receptor neurons. By constructing several olfactory bulb models of different size, we have shown that the size of the bulb network has an impact on its ability to process noisy information. We have also, through biochemical modelling, investigated the behaviour of the enzyme CaMKII which is known to be critical for early olfactory adaptation (suppression of constant odour stimuli).</p> / <p>Luktsystemet anses allmänt vara det äldsta sensoriska systemet. Det utvecklades för att upptäcka och analysera kemisk information i form av lukter, och det är organiserat efter samma principer hos nästan alla djurarter: insekter så väl som däggdjur. Troligen beror likheterna på parallell evolution -- samma organisation har uppstått mer än en gång. Därför antas det ofta att luktsystemet är nära optimalt anpassat för sina arbetsuppgifter. Paradoxalt nog är luktsystemets arbetssätt ännu inte väl känt, även om flera banbrytande framsteg gjorts de senaste decennierna. Det mest välkända är nog upptäckten av genfamiljen av luktreceptorer, som tillkännagavs 1991 av Linda Buck och Rikard Axel. För detta och efterföljande arbete belönades de med Nobelpriset år 2004. Upptäckten har varit mycket värdefull för både experimentalister och teoretiker, och formar grunden för vår nuvarande förståelse av luktsystemet. Luktsystemet har länge varit ett fokus för vetenskapligt intresse, både experimentellt och teoretiskt. Ända sedan fältet beräkningsbiologi grundades har luktsystemet undersökts genom datormodellering. I denna avhandling presenterar jag grunden för en biologiskt realistisk modell av luktsystemet. Vårt mål är att kunna representera hela luktsystemet. Så långt har vi ännu inte nått, men vi har några av de nödvändiga byggstenarna: en modell av signalerna från populationen av luktreceptorceller, och en modell av luktbulben. Genom att ta hänsyn till nervcellernas rapporterade variationer i geometriska, elektriska och receptor-beroende karaktärsdrag har vi lyckats modellera svarsfrekvenserna från en population av luktreceptorceller. Genom att konstruera flera olika stora modeller av luktbulben har vi visat att storleken på luktbulbens cellnätverk påverkar dess förmåga att behandla brusig information. Vi har också, genom biokemisk modellering, undersökt beteendet hos enzymet CaMKII, som är kritiskt viktigt för adaptering (undertryckning av ständigt närvarande luktstimuli) i luktsystemet.</p>

Face au manque de connaissances sur la mobilisation des compétences olfactives dans la vie quotidienne humaine et sur son développement, le premier objectif de cette étude était de développer un questionnaire d'Evaluation des Comportements OLfactifs de l'Enfant de 6 à 10 ans (ECOLE). Cet outil permet de mieux connaître l'écologie olfactive enfantine. Il révèle des caractéristiques psychométriques satisfaisantes et se montre en accord avec plusieurs autres mesures impliquant des odorants réels (réactivité hédonique aux odeurs plaisantes/déplaisantes, attention aux odeurs ambiantes). En revanche, le questionnaire ECOLE est faiblement lié à l'évaluation des comportements olfactifs par les parents, ce qui illustre l'idiosyncrasie et la faible verbalisation des comportements olfactifs quotidiens au sein de la famille. Un décalage existe également entre le questionnaire ECOLE et d'autres mesures olfactives (impact des odeurs en situation réelle, performances olfactives à un test standard). Ceci découle probablement de différences dans les mécanismes de traitements des odeurs impliqués (automatique ou conscient) et dans la signification du contexte. Le second objectif consistait à étudier les facteurs de variation interindividuelle des comportements et capacités olfactives chez l'enfant. (1) Les résultats révèlent une amélioration avec l'âge de la plupart des performances olfactives mesurées (score ECOLE, discrimination/identification des odeurs, impact hédonique des odeurs sur l'appréciation d'un objet). Cette amélioration est liée au développement cognitif général de l'enfant. (2) Bien qu'aucune différence de genre n'apparaisse dans le test olfactif standard, les filles se déclarent nettement plus attentives et réactives aux odeurs que les garçons dans le questionnaire ECOLE, et elles ont tendance à être plus affectées par l'impact implicite des odeurs ambiantes. L'expérience et le<br />contexte socioculturel semblent jouer un rôle dans l'établissement de ces différences. (3) Par ailleurs, certains traits de personnalité (évalués par les parents) sont liés à l'évaluation hédonique des odeurs par les enfants (plus positive chez les extravertis, plus négative chez les névrotiques et les néophobes alimentaires) et à la sensibilité olfactive (les extravertis sont moins sensibles). (4) Enfin, certains paramètres environnementaux, comme la diversité d'odeurs dans le cadre domestique, le sex-ratio familial, le niveau d'éducation et l'origine ethnique des parents, sont associés à des variations d'attention et de réactivité aux odeurs, 'identification et de sensibilité olfactives. Dans l'ensemble, cette étude contribue à montrer que, malgré sa réputation de microsmate, l'homme utilise les informations olfactives de son environnement et que cette utilisation est modulée de façon précoce par des facteurs individuels et environnementaux.

Multimodal sensory input directs simple and complex behaviors in animals. Most research to date has been limited to studies of individual senses rather than multiple senses working together, leading to important advances in our comprehension of the sensory systems in isolation, but not their complementary and alternative roles in difficult behavioral tasks, such as feeding. In the marine environment, a prey item might emit an odor, create a hydrodynamic disturbance, such as from gill movements or swimming, be visible to the predator, produce a sound, and/or produce a weak electrical field. Therefore, the goal of this study was to investigate the integration of olfaction, mechanoreception by the lateral line system, vision, and electroreception in a marine animal. Sharks were chosen as a model organism in which to investigate multisensory integration because of their sensitivity and acuity, the presence of the same suite of sensory modalities in all species, the availability of experimental animals from different species, habitats and ecologies, and the rich literature on sharks' prey capture behavior. Two approaches were used: controlled artificial stimuli, delivered to the animals, were used to determine the spatial and concentration characteristics of odor encounters that guide the initial orientation to an odor plume in the far field in a model elasmobranch, the smooth dogfish, Mustelus canis; and sensory deprivation was used to restrict the availability of natural cues emanating from live prey items in order to elucidate the complementary and alternating roles of the senses in detecting, tracking, orienting to, striking at, and ultimately capturing prey. In the latter experiments, three species of sharks from different ecological niches were investigated: benthic, suction-feeding nurse sharks (Ginglymostoma cirratum) that hunt nocturnally for fish; ram-biting bonnetheads (Sphyrna tiburo) that scoop crustaceans off the bottom of seagrass beds; and ram-feeding blacktip sharks (Carcharhinus limbatus) that rapidly chase down midwater teleost prey. In orienting to odor patches, bilateral time differences between the nares are more important than concentration differences, such that animals turn toward the side stimulated first, even with delayed pulses of higher concentration. This response would steer the shark into each oncoming odor patch, helping the animal maintain contact with an odor plume. Sensory deprivation experiments revealed similarities and differences among species in terms of which senses they choose to focus on for particular behaviors, likely as a result of differences in the environments that they hunt in, type of prey consumed, and foraging strategies used, as well as anatomical differences in the central nervous system and the sensory organs. In most cases, multiple senses can be used for the same behavioral task. Thus, sharks are capable of successfully capturing prey, even when the optimal sensory cues are unavailable, by switching to alternative sensory modalities, which indicates that feeding behavior is plastic. Nurse sharks rely primarily on olfaction for detection. Olfaction in combination with vision, the lateral line, or touch is required for tracking. Nurse sharks orient to prey using the lateral line, vision, or electroreception, but will not ingest food if olfaction is blocked. Capture is mediated by the electrosensory system or tactile cues. Bonnetheads normally detect prey using olfaction, rely on olfactory-based tracking until they are close to the prey, then vision to line up a strike, and finally electroreception to time the jaw movements for capture. They can detect, orient, and strike visually in the absence of olfactory cues. Blacktip sharks also detect prey using olfaction or vision. Olfaction is used in combination with vision or the lateral line system for tracking. Long-distance orientation and striking is visually mediated, but strike precision relies on lateral line cues and an increase in misses occurs when this system is blocked. In the absence of vision, short-range orientation and striking can occur using lateral line cues. Capture is mediated by electroreception or tactile cues. Collectively, these results were used to develop species-specific sensory hierarchies for shark feeding behavior in a captive environment, the first such hierarchies to cover a complete behavioral sequence in a vertebrate.

Signal transduction pathways mediated by G protein-coupled receptors (GPCRs) and their intracellular coupling partners, the heterotrimeric G proteins, are crucial for several physiological functions in eukaryotes, including humans. This thesis describes a broad genomic survey and extensive comparative phylogenetic analysis of GPCR and G protein families from a wide selection of eukaryotes. A robust mining of GPCR families in fungal genomes (Paper I) provides the first evidence that homologs of the mammalian families of GPCRs, including Rhodopsin, Adhesion, Glutamate and Frizzled are present in Fungi. These findings further support the hypothesis that all main GPCR families share a common origin. Moreover, we clarified the evolutionary hierarchy by showing for the first time that Rhodopsin family members are found outside metazoan lineages. We also characterized the GPCR superfamily in two important model organisms (Amphimedon queenslandica and Saccoglossus kowalevskii) that belong to different metazoan phyla and which differ greatly in morphological characteristics. Curation of the GPCR superfamily (Paper II) in Amphimedon queenslandica (an important model to understand evolution of animal multicellularity) reveals the presence of four of the five GRAFS families and several other GPCR gene families. However, we find that the sponge GPCR subset is divergent from GPCRs in other studied bilaterian and eumetazoan lineages. Mapping of the GPCR superfamily (Paper III) in a hemichordate Saccoglossus kowalevskii (an essential model to understand the evolution of the chordate body plan) revealed the presence of all major GPCR GRAFS families. We find that S. kowalevskii encodes local expansions of peptide and somatostatin- like GPCRs. Furthermore, we delineate the overall evolutionary hierarchy of vertebrate-like G protein families (Paper IV) and provide a comparative perspective with GPCR repertoires. The study also maps the individual gene gain/loss events of G proteins across holozoans with more expanded invertebrate taxon sampling than earlier reports. In addition, Paper V describes a broad survey of nematode chemosensory GPCR families and provides insights into the evolutionary events that shaped the GPCR mediated chemosensory system in protostomes. Overall, our findings further illustrate the evolutionary hierarchy and the diversity of the major components of the G protein-coupled receptor signaling system in eukaryotes.

Terrestrial salamanders of the genus Plethodon are among many vertebrates possessing both main olfactory and vomeronasal systems, which the Volatility Theory posits are for detection of volatile and soluble olfactory cues, respectively. Further recent work showing a high amount of convergence between the two olfactory subsystems at the level of the central nervous system suggests complementary or overlapping roles for them. This study examined the use of the olfactory subsystems in prey detection from the perspectives of behaviour and neurobiology. Red-backed salamanders, Plethodon cinereus, were observed in standardized behavioural assays with both volatile and soluble prey olfactory cues. Naïve salamanders showed an increase in nosetapping as well as a side preference in the presence of soluble and volatile prey cues when tested in a 22°C day/20°C night room. In a 15°C day /12°C night room, salamanders increased nosetapping in the presence of soluble prey cues. Salamanders showed a pattern of responses that differed based on their previous experience with the assay, as well as the temperature of the testing room. Attempts to study the neurobiology of olfactory function in Plethodon shermani were inconclusive up to this point, but future directions are discussed. This study shows the importance of olfaction in prey detection by salamanders and that prey searching behaviour is exhibited in the exclusive presence of olfactory cues.

La plupart des études sur la perception isolent une modalité sensorielle pour mieux l’étudier et la comprendre. Malheureusement, aucun de nos sens ne représente la seule source d’information, car une intégration sensorielle se fait en tout moment lors de la perception de l’environnement. L’information d’un sens est donc plutôt en accord ou en conflit avec l’apport d’information des autres sens. Le but de la présente étude était d’investiguer, par IRMf, les activations cérébrales d’une intégration visuelle et olfactive lorsque ces deux perceptions sont congruentes. Pour ce faire, une image et/ou une odeur étaient présentées au sujet et ce dernier devait identifier si le stimulus perçu était congruent. Ce protocole permettait d’observer les activations cérébrales lors de l’analyse d’un stimulus et la prise de décision selon la congruité du stimulus présenté. La condition de congruence vision-odeur activa les zones visuelles et olfactives plus fortement que lors des conditions contrôle (image seule, odeur seule). Ces résultats illustrent une potentialisation des aires visuelles et olfactives par une intégration d’information congruente venant de ces deux modalités. Par conséquent, l’intégration d’un stimulus visuel et odorant congruent semble rehausser la perception du stimulus. / Most studies on perception isolate one sensory modality in order to better study and comprehend it. Unfortunately, none of our senses represents the only source of information, since sensory integration is underway at all times during environmental perception. The information from one sense is therefore usually in agreement with or in conflict with the input of information from other senses. The goal of the present study was to investigate, by fMRI, the cerebral activations caused by visual and olfactory integration when these two perceptions are congruent. To do this, an image and/or an odour were presented to the subject who then had the task of identifying whether the perceived stimulus was congruent. This protocol allowed the observation of the cerebral activations during stimulus analysis and decision-making depending on the congruity of the presented stimulus. The vision-odour congruent condition activated the visual and olfactory areas more strongly than the control conditions (image only, odour only). These results illustrate a potentialization of the visual and olfactory areas by an integration of the congruent information coming from these two modalities. As a result, the integration of a visual and olfactory congruent stimulus seems to enhance the perception of a stimulus.