This dissertation is focused on how circadian control of olfactory responses are regulated at the cellular and molecular level in Drosophila. Electrophysiological approaches consisting of Electroantennogram (EAG), single unit recordings, among other techniques, were used to investigate the extent of autonomy of peripheral oscillators from central pacemaker cells, the molecular targets of the circadian oscillator in antennal neurons, and the nature of circadian influence on single unit responses recorded from basiconic sensillae. To address the question of cellular mechanisms mediating olfaction rhythms, UAS-Gal4 strategies were used for tissue specific expression of dominant negative forms of CLK (CLOCK) and CYC (CYCLE). Specifically, OR (Odorant Receptor)- GAL4 constructs were used to achieve cell specific expression in the antenna. By recording EAG responses from specific regions of the antenna, it was found that antennal sensory neurons possess independent oscillators that are both necessary and sufficient to drive rhythms in olfactory responses. To understand the molecular mechanisms controlling olfaction rhythms, the effect of GRK-2 and an arrestin (KURTZ) of the olfactory signal transduction pathway were studied by use of respective mutants and the effect of cell specific rescue of these proteins by UAS-Gal4 approaches was also documented. Interestingly, these molecules have phenotypes that argue for a different role of for these proteins in Drosophila olfaction as opposed to their respective functions in vertebrate systems. Finally, single unit recordings were measured from different basiconic sensilla and the influence of the circadian oscillator was studied on select parameters of the single unit data obtained. It was found that spike amplitude of the spontaneous response was the only parameter under circadian control and that these rhythms are dependant on input from the odorant receptor activated pathway.

Faulkner’s literature, set in the American South, imagines a rich olfactory environment. The ways in which characters employ their sense of smell provide information regarding the gender and racial stereotypes portrayed and maintained within Faulkner’s fictional communities. In my texts of focus, these communities are often characterized by misogyny, conservatism, and Christian piety. Within these narrow minded communities, an exploration of Faulkner’s olfactory landscape is important in order to examine how olfactory stimuli are interpreted and applied to the marginalized female and racially coded body. In Faulkner’s literature, smells appear to trigger male anxieties concerning the female body, anxieties related to sexuality and racial misrecognition, and scent is largely correlated to the objectification of female characters in a manner comparable to the male gaze.

The nervous system copes with variability in the external and internal environment by using neuromodulators to adjust the efficacy of neural circuits. The role of serotonin (5HT) as a neuromodulator of olfactory processing in the antennal lobe (AL) of Manduca sexta was examined. Serotonin has been hypothesized as a circadian modulator of sensitivity of AL neurons, so the coding of odor concentration in the AL was first examined without the manipulation of 5HT levels. Reponses of the AL to different concentrations of odors were recorded using multi-electrode extracellular arrays. As odor concentration increased, more AL units responded and the AL was best able to discriminate odors at high concentrations, a finding that was replicated in matched behavioral assays. Multi-electrode recordings were then used to examine the effects of 5HT on responses to stimuli that varied in chemical structure and concentration. Serotonin enhanced AL unit responses by increasing response duration and firing rate, which in turn increased the amount of coincident firing between units. Due to the increased activation of units as concentration increased, and the greater effect of 5HT on stronger responses, serotonin had the greatest effect on overall ensemble activation at higher odor concentrations. Additionally, response thresholds shifted to lower odor concentrations for some units, suggesting that 5HT increases the sensitivity of AL units. Serotonin enhanced AL discrimination of single odors at different concentrations and structurally dissimilar odors at a single concentration. In order to predict which insects share a similar role for 5HT in the AL, immunocytochemistry was used to compare the ALs of different insects. All holometabolous insects (except the Euhymenoptera) had 5HT-immunoreactive AL neurons that were morphologically similar to those of M. sexta. These combined studies implicate 5HT as a modulator of sensitivity and efficacy in the AL of M. sexta and suggest that 5HT may play this role for most of the Holometabola. This proposed role of 5HT in the AL of the Holometabola is reminiscent of the hypothesized involvement of serotonergic neurons from the Raphe nucleus in vertebrates that seem to gate activity in the olfactory bulb in the context of behavioral arousal.

No description available.

Understanding how odors are encoded in the brain is of fundamental importance to neurobiology. The first two stages of olfactory information processing have been relatively well studied in both vertebrates and invertebrates. However, the organizational principles of higher order olfactory representations remain poorly understood. Neurons in the first relay of the olfactory system segregate into glomeruli, each corresponding to an odorant receptor. Higher-order neurons can receive input from multiple glomeruli, but it is not clear how they integrate their inputs and generate stimulus selectivity.

Nitric oxide (NO) is a gaseous, unconventional chemical messenger suggested to play a fundamental role in olfaction. This thesis focuses on the role of NO in a primary olfactory center, the antennal lobe (AL) of the moth, Manduca sexta (M. sexta), to understand how NO affects olfactory-guided behavior. Studies in M. sexta report that NO is produced upon odor stimulation and has profound effects at the physiological level, but little is known about its significance to behavior. The central hypothesis examined in this thesis is that NO functions as a neuromodulator of olfactory-guided behavior in a circadian fashion. This hypothesis is examined in the following three studies: The first study questions whether basal levels of NO fluctuate with the light cycle. M. sexta are nocturnal animals that actively engage in odor-seeking behaviors at night. Using an NO sensor, NO concentrations were measured in the AL, optic lobe, and the remainder of the brain during subjective day and subjective night. NO concentrations are higher in the AL and optic lobes at night, suggesting that NO is likely involved in olfactory-guided behavior. The second inquiry focuses on developing a technique to manipulate NO levels in the AL and whether a specific behavior is affected. Using the proboscis extension reflex, olfactory conditioning is used to ask three questions: (1) does NO affect odor detection, (2) does NO affect discrimination between odorants, and (3) does NO affect learning and memory? Results indicate that NO affects short-term memory but does not affect odor detection, or discrimination between dissimilar odorants. The third inquiry examines the role of NO in memory and circadian time. It asks: (1) is there an optimal time of day for learning and memory, and (2) does the role of NO in memory change depending on the time of olfactory conditioning? Results indicate that NO in memory is modulated by circadian time. Taken together, these results suggest a unique functional role for NO in olfactory-guided behavior with two main conclusions: (1) NO modulates short-term memory in the AL, and (2) NO may be important for the circadian regulation of memory.

No description available.

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.

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

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.