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). / 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.

Chemical sensing is believed to be the oldest sensory ability. The chemical senses, olfaction and gustation, developed to detect and analyze information in the form of air- or waterborne chemicals, to find food and mates, and to avoid danger. The organization of the olfactory system 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 seems to have 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 within several fields, both experimental and theoretical, and it has often been used asa model system. And 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 several approaches to biologically realistic computational models of parts of the olfactory system, with an emphasis on the earlier stages of the vertebrate olfactory system – olfactory receptor neurons (ORNs) and the olfactory bulb (OB). I have investigated the behaviour of the enzyme CaMKII, which is known to be critical for olfactory adaptation (suppression of constant odour stimuli) in the ORN, using a biochemical model. By constructing several OB models of different size, I have shown that the size of the OB network has an impact on its ability to process noisy information. Taking into account the reported variability of geometrical, electrical and receptor-dependent neuronal characteristics, I have been able to model the frequency response of a population of ORNs. I have used this model to find the key properties that govern most of the ORN population’s response, and investigated some of the possible implications of these key properties in subsequent studies of the ORN population and the OB – what we call the fuzzy concentration coding hypothesis. / Detektion av kemiska ämnen anses allmänt vara den äldsta sensoriska förmågan. De kemiska sinnena, lukt och smak, utvecklades för att upptäcka och analysera kemisk information i form av luft- eller vattenburna ämnen, för att hitta mat och partners, och för att undvika fara. Luktsystemet är organiserat efter samma principer hos nästan alla djurarter, insekter såväl som däggdjur. Troligen beror likheterna på parallell evolution – samma organisation verkar ha uppstått mer än en gång. Därför antas det ofta att luktsystemet är nära optimalt anpassat för sina arbetsuppgifter.Paradoxalt nog är luktsystemets arbetsprinciper ännu inte väl kända, 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 är grunden för vår nuvarande förståelse av luktsystemet. Luktsystemet har länge varit ett fokus för vetenskapligt intresse inom flera fält, experimentella såväl som teoretiska, och har ofta använts som ett modellsystem. Och ända sedan fältet beräkningsneurobiologi grundades har luktsystemet undersökts genom datormodellering. I denna avhandling presenterar jag flera ansatser till biologiskt realistiskaberäkningsmodeller av luktsystemet, med tonvikt på de tidigare delarna av ryggradsdjurens luktsystem – luktreceptorceller och luktbulben. Jag har undersökt beteendet hos enzymet CaMKII, som anses vara kritiskt viktigt för adaptation (undertryckning av ständigt närvarande luktstimuli) i luktsystemet, i en biokemisk modell. Genom att konstruera flera olika stora modeller av luktbulben har jag visat att storleken på luktbulbens cellnätverk påverkar dess förmåga att behandla brusig information. Genom att ta hänsyn till nervcellernas rapporterade variationer i geometriska, elektriska och receptor-beroende karaktärsdrag har jag lyckats modellera svarsfrekvenserna från en population av luktreceptorceller. Jag har använt denna modell för att hitta de nyckelprinciper som styr huvuddelen av luktreceptorneuron-populationens svar, ochundersökt några av de tänkbara konsekvenserna av dessa nyckelprinciper i efterföljande studier av luktreceptorneuron-populationen och luktbulben – det vi kallar ”fuzzy concentration coding”-hypotesen. / QC20100723

No description available.

The mitral cells of the accessory olfactory bulb (AOB) of anuran frogs project their axons directly to the medial amygdala (MeA) along the accessory olfactory tract. An en bloc preparation of the telencephalon of the American bullfrog Lithobates catesbeiana was utilized to study a form of low-frequency inducible long-term potentiation (LTP) expressed at the synapse formed between the terminals of the accessory olfactory tract and the neurons of the MeA. Delivery of repetitive 1Hz-stimulation or sets of 5Hz tetani to the accessory olfactory tract both induced potentiation that was stable for over an hour, as measured by extracellular field recordings. LTP induced by 5Hz tetanus was associated with a decrease in paired-pulse ratio, which would be consistent with an increased probability of release contributing to the increased synaptic strength. Blockade of neither NMDA nor kainate glutamate receptors, with AP5 and UBP310 respectively, prevented LTP induction by 5Hz tetanus; however expression of LTP was partially masked in the presence of UBP310. These results suggest that kainate receptors are involved in the expression of LTP at the AOB-MeA synapse, though the means by which LTP is induced remains unclear. / Graduate / 2016-09-28

Cranial placodes are transient thickenings of the vertebrate embryonic head ectoderm that will give rise to sensory (olfactory, lens, and otic) and non-sensory (hypophyseal) components of the peripheral nervous system (PNS). In most vertebrate embryos, these four sensory placodes undergo invagination. Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures, like an epithelial pit/cup. The process of invagination is crucial during development as it plays an important role for the formation of the lens, inner ear, nasal cavity, and adenohypophysis. Using the chick as the model system the following questions were addressed. What signals are involved in placode invagination? Is there any common regulatory molecular mechanism for all sensory placode invagination, or is it controlled by unique molecular codes for each individual placode? Are placode invagination and acquisition of placode-specific identities two independent developmental processes or coupled together? To address this we used in vivo assays like electroporation and whole embryo culture. Our in vivo results provide evidence that RhoA and F-actin rearrangements, apical constriction, cell elongation and epithelial invagination are regulated by a common BMP (Bone morphogenetic protein) dependent molecular mechanism. In addition, our results show that epithelial invagination and acquisition of placode-specific identities are two independent developmental processes. BMP signals have been shown to be essential for lens development and patterning of the retina. However, the spatial and temporal requirement of BMP activity during early events of lens development has remained elusive. Moreover, when and how retinal cells are specified, and whether the lens plays any role for the early development of the retina is not completely known. To address these questions, we have used gain- and loss-of-function analyses in chick explant and intact embryo assays. Here, we show that during lens development BMP activity is both required and sufficient to induce the lens specific marker, L-Maf. After the L-Maf upregulation the cells are no longer dependent on BMP signaling for the next step of fiber cell differentiation, which is characterized by up-regulation of δ-crystallin expression. Regarding the specification of retinal cells our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character. Furthermore, from optic vesicle stages, BMP signals emanating from the lens are essential for maintaining eye-field identity, inhibiting telencephalic character and inducing neural retina cells.

The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is an integral component of the mouse accessory olfactory system, and plays a key role in pheromonal processing. In males, this region is not only larger and contains more neurons than in females, but the cells are also larger. The present study examined the relationship between preference for opposite-sex odour and regional volume, cell number and cell size within the BNSTp of both male and female mice. No correlations were found between olfactory preferences and any of the three morphological BNSTp parameters. However, the olfactory preference task results were not congruent with previous research. Therefore, it remains inconclusive whether relationships exist between olfactory preference behaviour and morphology of the BNSTp.

The earliest stage of Alzheimer’s disease (AD) pathology begins in one of the main components of the olfactory pathway, the entorhinal cortex, making deficits in smell a potential prospective biomarker for the early detection of AD. This study contributes to the field with a reproduction and extension of work by Wilson, Arnold, Schneider, Boyle, Buchman, and Bennett (2009). A sample of 1089 individuals (M=78.4 years), more than double the data available in 2009, completed annual assessments of olfactory functioning, and cognitive functioning for up to 18 years with brain donation at death. Mixed effects models conditioned on demographics estimated between and within-person effects in olfactory functioning and episodic memory (EM). After successful reproduction of Wilson et al. (2009), addition of AD pathology (ADP) demonstrated that both ADP and olfaction were significantly related to EM at baseline. Higher ADP at autopsy was significantly related to faster declines in olfaction, as well as more rapid declines in EM. Higher olfactory scores were associated with higher EM scores and a model for EM with olfaction as time-varying covariate indicated that at a given occasion, individuals with higher olfactory scores also have higher EM scores. These results align with the hypotheses that difficulty in identifying odors predicts development of cognitive impairment; increased levels of AD pathology are related to both decreased EM at baseline and faster declines, as well as faster rates of decline in olfaction; and olfaction and cognition are travelling together over time. / Graduate / 2018-06-01 / 0766 / 0633 / jknight@uvic.ca

No description available.

The role of Ca++ in olfactory responses was investigated with inorganic and organic calcium channel antagonists. Electrophysiological responses to odorants were recorded from frog olfactory mucosa before and after aerosol application of different agents. Electroolfactogram responses were blocked by certain inorganic ions with the order of effectiveness Zn++ >Ln+++>Cd++>Ca++>Co++>Sr++>Mg++. Ba++ potentiated olfactory responses, and is known to potentiate calcium channel-mediated responses in other tissues. Certain local anesthetics which are thought to act through calcium channel blockade were inhibitory to olfactory responses, with the order of effectiveness being dibucaine>tetracaine>procaine. These data support the idea that Ca++ is involved in olfaction, perhaps acting as a current carrier and/or a second messenger. Preliminary experiments on channel localization were performed using a silicon-labeled amine. Attempts to localize the silicon label were inconclusive, although silicon was detected in the olfactory tissue.

No description available.