With covid-19 affecting people's ability to smell, it might be of interest to find multimodal solutions, where other senses could assist someone with an impaired sense of smell to identify an odor. This area of research lacks data since there has not been many studies on this. Moreover, there are studies that tried to find a connection between sound and smell in other contexts. The goal of this study was to find if it is possible to communicate an odor, with the help of foley sound, to someone with an impaired sense of smell. This required answers to questions regarding whether people, with and without a changed sense of smell, can improve their odor identification with the help of sound and if foley is an effective method for it. This was tested by first collecting sound associations to odors, as well as cultural associations. The data were analyzed to find common themes to choose the sounds that would be used. The participants in the study were asked to make free identifications after being presented with odor pens together with additional stimuli cues. The experiment included tests with an associated color, a matching foley sound, a matching soundscape, an incongruent color and an incongruent foley sound. The results showed that sound in general has a positive impact on someone's identification capabilities, which were measured by counting the amount of right answers on each test. The odors coffee, fish and leather had foley sound that greatly increased the amount of correct answers whilst the foley sound to lemon, rose and peppermint had less of an impact. People with an imparied sense of smell were affected similarly to the different stimuli as people without an impairment. Since identification of odors are dependent on prior experiences, some odors could be harder or easier to identify. In order to create an auditory icon for an odor there needs to be strong collective associations for it to be efficient in relaying information and not being distracting. / Covid-19 har haft en negativ effekt på människors förmåga att känna lukt, och därmed finns det ett intresse av att undersöka och hitta multimodala lösningar där andra sinnen kan hjälpa att identifiera en lukt. Det har inget större omfång av liknande forskning inom detta område. Däremot finns det studier som försökt hitta en koppling mellan ljud och lukt i andra kontexter. Målet med denna studie var att ta reda på ifall ljud kunde hjälpa att kommunicera en lukt för någon med försämrat luktsinne. Detta innebar att besvara frågor huruvida foleyljud kan förbättra människors luktidentifieringsförmåga, både för dem med nedsatt luktförmåga och oförändrat luktsinne. Det innebar också att testa ifall foleyljud är effektivare än andra typer av ljud. Forskningsfrågorna testades genom att först samla in ljud associationer till olika lukter, samt kulturella associationer. Datan analyserades för att hitta gemensamma teman att göra ljud av. Deltagarna i studien ombads skriva fria identifieringar efter att ha presenterats med doftpennor, samtidigt som de utsattes för ett annat stimulus. De stimulikombinationer som testades var doft med associerad färg, doft med ett tillhörande foleyljud, doft med en tillhörande ljudbild, samt versioner med inkongruent färg och inkongruent foleyljud. Resultatet visar att ljud har en positiv påverkan på personers identifieringsförmåga, vilket mättes med hur många som skrev rätt doft på varje test. Lukterna kaffe, fisk och läder hade foleyljud som ökade antalet rätta svar medan foleyljud till lukterna citron, ros och pepparmynta hade en mindre påverkan. Personer med nedsatt luktsinne påverkades på liknande sätt av de olika testerna som folk utan påverkan. Då luktperception påverkas av tidigare erfarenheter kan olika lukter vara svårare eller lättare att identifiera. För att lukt ska kunna sonifieras behövs starka kollektiva associationer som är tillräckligt kända för att lättare förmedla information och inte distrahera lyssnaren.

published_or_final_version / Electrical and Electronic Engineering / Master / Master of Philosophy

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Le bulbe olfactif est le siège d’une neurogenèse adulte permanente. Le nombre de nouveaux neurones issus de cette neurogenèse adulte est modulé par l’apprentissage, ce qui suggère un rôle des néoneurones dans la mémoire olfactive. Au cours de ce travail, nous avons montré que l’apprentissage olfactif associatif recrute des nouveaux neurones granulaires dans des régions de la couche granulaire du bulbe olfactif spécifiques à l’odeur apprise. Nous avons également mis en évidence un lien entre la force de l’apprentissage olfactif, sa rétention et la modulation de la neurogenèse qui en résulte. En bloquant la neurogenèse bulbaire à l’aide d’un agent antimitotique nous avons montré que les nouveaux interneurones ne sont pas indispensables à l’acquisition d’une tâche olfactive associative, mais le sont pour sa rétention à long terme. Puis, en utilisant une approche comportementale, nous avons aboli l’association olfactive acquise lors d’un apprentissage et nous avons observé que les nouveaux neurones initialement sauvés dans le bulbe olfactif par cet apprentissage disparaissaient prématurément, confirmant ainsi leur rôle dans le support de la mémoire olfactive. Enfin, nous avons montré que suite à un apprentissage olfactif, une régulation locale de la mort cellulaire est mise en jeu qui pourrait être à l’origine de la sélection des néoneurones dans les régions traitant l’odeur apprise. Dans l’ensemble nos données indiquent un rôle crucial des neurones formés à l’âge adulte dans le bulbe olfactif dans la mémoire olfactive / Adult-born neurons are added to the mammalian olfactory bulb, and their number is modulated by learning suggesting that they could play a role in olfactory memory. In this work, we demonstrate that retrieval of an associative olfactory task recruits newborn neurons in odor-specific areas of the olfactory bulb and in a manner that depends on the strength of learning. By blocking neurogenesis during this olfactory task, we then demonstrate that acquisition is not dependent on neurogenesis while long-term retention of the task is abolished by neurogenesis blockade. In a second part, using an ecological approach, we show that behaviorally breaking a previously learned odor-reward association prematurely suppresses newborn neurons selected to survive during initial learning. Our results indicate that the newborn neurons saved by olfactory learning die when the odor looses its associative value, thus confirming that these newborn neurons support the memory trace. Finally, during and after learning, cell death and BrdU positive cells were mapped in the granule cell layer. We find that regions showing high BrdU-positive cell density exhibit the lowest rate of cell death indicating local regulation of cell death shaping the spatial distribution of newborn neurons in the granule cell layer of the olfactory bulb. Taken together, our findings reveal the crucial role of bulbar adult born neurons in olfactory memory

Olfactory ensheathing cells (OECs), the glia of the olfactory nerve, are promising candidates for patient-specific cell-mediated repair of both peripheral nerves and the spinal cord. The recent discovery that OECs originate from the neural crest, rather than the olfactory epithelium as previously thought, potentially means that homogeneous populations of OECs for repair could be expanded in culture from neural crest stem cells persisting in the patient's own skin and hair follicles. The first step towards this long-term goal is to understand the molecular mechanisms underlying neural crest differentiation into OECs, as opposed to Schwann cells (the glia of all other peripheral nerves), which are less effective in spinal cord repair. To identify transcription factors and signalling pathways that might be involved in OEC versus Schwann cell differentiation, I took an unbiased transcriptome profiling approach. Taking advantage of Sox10 expression throughout both OEC and Schwann cell development, I used laser-capture microdissection on cryosections of mouse embryos carrying a Sox10:H2BVenus transgene, to isolate OEC subpopulations (olfactory mucosal OECs, from the olfactory nerve, and olfactory nerve layer OECs, from the olfactory nerve layer surrounding the olfactory bulb) at different stages of development, and Schwann cells from trigeminal nerve branches on the same sections, for RNA-seq and cross-wise comparison of transcriptomes. Validation of candidate genes by in situ hybridisation revealed some contamination with adjacent cells from mesenchyme, olfactory epithelium or olfactory bulb, but also identified the expression in developing OECs of various genes previously reported to be expressed in adult OECs, and of over 20 genes previously unknown in OECs. Some of these genes are expressed by OECs but not Schwann cells; some are expressed by olfactory nerve layer OECs but not olfactory mucosal OECs, while some are expressed by olfactory mucosal OECs and Schwann cells but not olfactory nerve layer OECs. For a subset of the genes, I was also able to analyse OEC differentiation in mouse mutants. I also collected transcriptome data from neural crest-derived cells that persist on the olfactory nerve in Sox10-null embryos (in which neural crest-derived cells colonise the olfactory nerve, but normal OEC differentiation is disrupted). Comparison with wild-type OEC transcriptome data from the same embryonic stage identified genes whose expression is likely either downregulated or up-regulated in the absence of Sox10, supporting a role in normal OEC differentiation. Overall, these various transcriptomic comparisons (between OECs at different developmental stages, different OEC subpopulations, OECs versus Schwann cells, and OECs versus Sox10-null neural crest-derived cells on the olfactory nerve) have identified multiple transcription factor and signalling pathway genes, amongst others, that are expressed during OEC development in vivo (including some specific to different OEC subpopulations) and that may be important for OEC differentiation. Furthermore, some of these genes are not expressed by embryonic Schwann cells. This work provides a foundation for understanding how to promote OEC rather than Schwann cell differentiation from neural crest stem cells in culture, with the potential for clinical application in the future.

The clustered protocadherins (Pcdh α, β & γ) provide individual neurons with cell surface diversity. However, the importance of Pcdh mediated diversity in neural circuit assembly and how it may promote neuronal connectivity remains largely unknown. Moreover, to date, Pcdh in vivo function has been studied at the level of individual gene clusters; whole cluster-wide function has not been addressed. Here I examine the role of all three Pcdh gene clusters in olfactory sensory neurons (OSNs); a neuronal type that expressed all three types of Pcdhs and in addition I address the role of Pcdh mediate diversity in their wiring. When OSNs share a dominant single Pcdh identity (α, β & γ) their axons fail to form distinct glomeruli, suggestive of inappropriate self-recognition of neighboring axons (loss of non-self-discrimination). By contrast, deletion of the entire α, β,γ Pcdh gene cluster, but not of each individual cluster alone, leads to loss of self-recognition and self-avoidance thus, OSN axons fail to properly arborize. I conclude that Pcdh-expression is necessary for self-recognition in OSNs, whereas its diversity allows distinction between self and non-self. Both of these functions are required for OSNs to connect and assembly into functional circuits in the olfactory bulb. My results, also reveal neuron-type specific differences in the requirement of specific Pcdh gene clusters and demonstrate significant redundancy between Pcdh isoforms in the olfactory system.

The cerebral cortex continuously encodes new sensory information and organizes it within an experiential intracortical framework. The cortical integration of internal and external information forms the associations that are the basis for higher order sensory representation, and ultimately, perception. Deciphering the cellular and synaptic principles of sensory-cortical integration requires a system with a simplified interface between the internal and external worlds. The piriform cortex provides a relatively simple substrate for the study of intracortical modulation of sensory coding. Within piriform, primary sensory information from the olfactory bulb converges onto neurons in a single cortical layer, where it directly integrates with intracortical input. The major barrier to studying intracortical influences on sensory representation in piriform has been the inability to isolate single types of intracortical input. Here, we use optogenetic techniques to functionally isolate two important classes of intracortical input to piriform pyramidal neurons, and slice electrophysiology to assess their synaptic properties. We first expressed channelrhodopsin in a small subset of piriform neurons, effectively isolating the recurrent synapses formed onto piriform pyramidal neurons by their peers. Recurrent collaterals form strong excitatory connections that extend throughout piriform without spatial attenuation in strength, linking distant piriform neurons. This extensive recurrent network is constrained by powerful disynaptic inhibition, which can also reduce activation by primary sensory inputs in a timing-dependent manner. Next, we functionally isolated inputs to the piriform from the anterior olfactory nucleus (AON), an early target of olfactory bulb output whose role in olfaction is largely unknown. The AON makes weaker excitatory connections with piriform, but unlike recurrent connections, these inputs do not drive strong disynaptic inhibition. Sequential activation of AON inputs leads to pronounced summation that boosts piriform activation in an NMDA-receptor-dependent manner, and may enhance plasticity of AON-to-piriform synapses. The AON is a potentially powerful modulator of piriform cortex, whose role in odor information processing merits further study. Our results collectively illustrate critical features of intracortical input classes to piriform cortex, and how these inputs may have distinct roles in shaping odor representations and olfactory learning.

The mushroom body (MB) is the site of odor association learning in Drosophila.  In the canonical model, there are two types of reinforcing dopamine neurons (DANs): one set for rewarding unconditioned stimuli (US), and one responding to aversive US.  When DANs are activated together with an odor (the conditioned stimulus, or CS), plasticity is induced in the downstream output neurons (MBONs).  We have identified a DAN (V1) that surprisingly responds preferentially to odors, and responds weakly or not at all to various classical US.  In order to explore the relationship between V1 odor responses and the established roles of the MB, I characterized the responses of DAN V1, and probed its relationship to odor-driven behavior, associative conditioning, and activity in other MB compartments. These data show that V1 receives recurrent input from identified MBONs, contributes to the activity of an MBON that enhances alerting behavior, and that its odor responses are modulated by conditioning. We therefore present the study of the alpha2 compartment, which V1 innervates, as the dissection of an atypical compartment of the MB, one that acts as a hub by which various information from other compartments and brain areas is integrated in order to alter a behavioral response to odor. This work furthers our understanding of the MB not simply as an engine of classical learning, but as a system of diverse interconnected modules that allow coordinated fine control of behavior.