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The widely accepted view nowadays is that experiencing odours as rather pleasant or unpleasant is, to a certain degree, shaped on a daily basis through individual experience within one's culture via evaluative conditioning or, rather marginally so, via mere exposure to that certain odour. In other words, humans are not born with any fixed set of olfactory likes or dislikes but rather, they acquire them throughout their lifetime. However, olfactory sensation is not a "pure" percept, as odorant stimuli generally elicit a qualitative percept of an odorant - generated mainly by the olfactory nerve - as well as some degree of chemesthesis - a tactile confound of the odour generated mainly by the trigeminal nerve. The olfactory and trigeminal system exhibit complex interactions at both the peripheral and central level of chemosensory processing, which is also reflected in perceptual characteristics of the final percept, including perceived pleasantness (hedonics). If the olfactory contribution alone does not easily predict neonatal odour hedonics, due to newborns' limited previous exposure to chemosensory inputs, one may hypothesize that together with the strength of the trigeminal contribution they may form a significant factor affecting neonatal appetitive/aversive responses to odours. In the present...

Les figures de neuroanatomie de ce mémoire peuvent être téléchargées en haute résolution. / Une voie neuronale sous-tendant la locomotion induite par la détection d’odorants a été découverte chez la lamproie (Derjean et al., 2010). Le signal olfactif est relayé du bulbe olfactif médian au tubercule postérieur, puis à la région locomotrice mésencéphalique et enfin aux cellules réticulospinales qui activent les réseaux locomoteurs spinaux. Des études récentes démontrent que le bulbe olfactif médian est sous l’influence d’une inhibition GABAergique tonique qui régule les réponses des cellules réticulospinales à la stimulation du nerf olfactif (Daghfous et al., 2013). Des mécanismes de modulation supplémentaires pourraient exister dans le bulbe olfactif de Petromyzon marinus puisqu’il contient aussi des fibres dopaminergiques. Chez tous les vertébrés étudiés, la dopamine joue un rôle important dans le traitement olfactif. Des techniques anatomiques (traçage et immunofluorescence) et physiologiques (enregistrements intracellulaires) ont été utilisées pour étudier la modulation dopaminergique de la voie olfacto-motrice. L’immunofluorescence ciblant la dopamine a révélé des fibres plus nombreuses dans la partie médiane du BO et à proximité de neurones de projection et de fibres olfactives. De plus, aucun corps cellulaire immunopositif n’a été détecté dans le bulbe olfactif. L’enregistrement des réponses synaptiques des cellules réticulospinales à la stimulation du nerf olfactif a été réalisé dans le cerveau isolé in vitro. L’injection locale de dopamine dans le bulbe olfactif médian diminue de moitié l’amplitude de réponse. Sous l’effet d’un antagoniste des récepteurs GABAA dans le bain ou localement dans le bulbe olfactif médian, les dépolarisations soutenues enregistrées sont supprimées par l’injection de dopamine. Cependant, l’injection individuelle ou combinée dans le bulbe olfactif médian d’antagonistes sélectifs des récepteurs D1 ou D2, soit le SCH 23390 et l’éticlopride, demeure sans effet significatif sur les réponses olfacto-motrices, indiquant l’absence d’activité dopaminergique tonique. Pour localiser les neurones responsables de cette modulation, des injections de traceur axonal ont été combinées avec l’immunofluorescence ciblant la dopamine. Des cellules dopaminergiques projetant au BO médian ont été observées dans les noyaux dopaminergiques du tubercule postérieur et de l’hypothalamus périventriculaire. Dans l’ensemble, nos résultats montrent anatomiquement et physiologiquement la présence d’une innervation dopaminergique dans le bulbe olfactif médian qui a une action inhibitrice sur le traitement olfacto-moteur. / A neural substrate underlying odor-evoked locomotion was revealed in lampreys (Derjean et al., 2010), involving a neural pathway extending from the medial part of the olfactory bulb to the posterior tuberculum. The signal is then relayed to the mesencephalic locomotor region and eventually reaches reticulospinal cells that activate the spinal locomotor networks. Recent research in the lab (Daghfous et al., 2013) shows that the medial olfactory bulb, is under a tonic GABAergic inhibition gating reticulospinal cell responses to olfactory nerve stimulation. Additional modulatory mechanisms might exist in the olfactory bulb of Petromyzon marinus as it also contains dopaminergic fibers. In every vertebrate studied to date, dopamine plays an important role in olfactory processing. Anatomical (axonal tracers and immunofluorescence) and physiological (intracellular recordings) techniques were used to investigate the dopaminergic modulation of the olfacto-motor pathway. Dopamine immunofluorescence showed scarce innervation of the olfactory bulb that was most abundant in the medial part and in close vicinity to projection neurons and olfactory nerve fibers. Additionally, no dopamine-immunoreactive cell bodies were detected in the olfactory bulb. Synaptic responses of reticulospinal cells to olfactory nerve stimulation were recorded in the isolated brain. Local injection of dopamine in the medial olfactory bulb induces an almost two-fold decrease of the synaptic responses. When GABAA receptor antagonist GABAzine was also injected in the medial olfactory bulb, the effect of dopamine was much more evident and could suppress large bursts of action potentials. However, D1 (SCH 23390) and D2 (Eticlopride) receptor antagonists injection in the medial olfactory bulb failed to alter the amplitude of reticulospinal cell responses to olfactory nerve stimulation, indicating that this modulation is not tonic. To locate the neurons responsible for this modulation, tracer injections combined with dopamine immunofluorescence were performed. Dopaminergic cells projecting to the medial olfactory bulb were found in the dopaminergic nuclei of the posterior tuberculum and the periventricular hypothalamus. Altogether, our results show anatomically and physiologically the presence of a dopaminergic innervation within the medial olfactory bulb that mediates inhibitory effects on olfacto-motor signaling.

Les informations olfactives sont connues pour leur capacité à induire des comportements moteurs spécifiques. En dépit de nombreuses observations comportementales chez les vertébrés, on ne connaît toujours pas les mécanismes et les voies nerveuses qui sous-tendent ces phénomènes de transformation olfacto-locomotrices. Chez la lamproie, des travaux récents ont permis de décrire cette voie, et les mécanismes responsables de la transformation des entrées olfactives en activité locomotrice (Derjean et al., 2010). Cette voie prend origine dans la partie médiane du bulbe olfactif, et envoie des projections vers le tubercule postérieur, une région qui se trouve dans le diencéphale. De là, les neurones projettent directement vers la Région Locomotrice Mésencéphalique, connue pour envoyer des connexions vers les neurones réticulospinaux, et activer la locomotion. L’objectif de cette étude était d’établir si l’ensemble des neurones réticulospinaux répond aux stimulations olfactives. Pour ce faire, nous avons utilisé sur une préparation de cerveau isolé de lamproie des techniques d’électrophysiologie et d’imagerie calcique. La stimulation électrique des nerfs olfactifs, de la région médiane du bulbe olfactif ou du tubercule postérieur a provoqué une activation de toutes les cellules réticulospinales qui se retrouvent dans les quatre noyaux réticulaires (ARRN : Noyau Réticulaire Rhombencéphalique Antérieur; MRN : Noyau Réticulaire Mésencéphalique; MRRN : Noyau Réticulaire Rhombencéphalique Moyen; PRRN : Noyau Réticulaire Rhombencéphalique Postérieur). Seule la partie médiane du bulbe olfactif est impliquée dans le passage de l’information olfactive vers les neurones réticulospinaux. Nous avons aussi découvert que le blocage des récepteurs GABAergiques dans la partie médiane du bulbe olfactif augmentait les réponses olfactives de façon considérable dans les cellules réticulospinales. Nous avons montré ainsi qu’il existe un tonus inhibiteur impliqué dans la dépression modulatrice de la voie olfacto-locomotrice. Ce travail a permis de montrer que la stimulation des afférences sensorielles olfactives active simultanément l’ensemble des populations de neurones réticulospinaux qui commandent la locomotion. De plus, il existerait un tonus inhibiteur GABAergique, au niveau de la partie médiane du bulbe olfactif, responsable d’une dépression modulatrice dans la voie olfacto-locomotrice. / Olfactory inputs are known for their ability to induce specific motor behaviors. Despite numerous behavioral observations in vertebrates, the mechanisms and the neural pathways underlying the olfactory-locomotor transformation are still unknown. In lamprey, recent studies have described this pathway and the mechanism underlying the transformation of olfactory input into a locomotor activity (Derjean et al., 2010). This pathway originates in the medial part of the olfactory bulb, sends projections to the posterior tuberculum, a diencephalic region. From there, the neurons project directly to the mesencephalic locomotor region that is known to send projections to the reticulospinal neurons to activate locomotion. Using lamprey brain preparation, electrophysiology and calcium imaging, the aim of this study was to establish whether all reticulospinal neurons respond to olfactory stimuli. Electrical stimulation of the olfactory nerves, the medial part of the olfactory bulb or the posterior tuberculum activates all reticulospinal cells in the four reticular nuclei (ARRN: Anterior rhombencephalic reticular nucleus; MRN: middle mesencephalic reticular nucleus; MRRN: middle rhombencephalic reticular nucleus; PRRN: posterior rhombencephalic reticular nucleus). The medial part of the olfactory bulb is the only region that is implicated in transmitting the olfactory information to reticulospinal neurons. We also discovered that when blocking the GABAergic receptors in the medial part of the olfactory bulb, the reticulospinal neurons have a stronger response to olfactory stimulation. Thus we showed that a tonic inhibition is involved in the modulating depression of the olfacto-locomotor pathway. Altogether, this work shows that stimulation of the olfactory sensory inputs activates simultaneously the entire population of reticulospinal neurons that control locomotion. In addition, there is a GABAergic tonic inhibition at the level of the medial part of the olfactory bulb that causes a modulating depression in the olfacto-locomotor pathway.

INTRODUÇÃO: Apesar da fundamental importância da olfação para avaliação dos sabores dos alimentos ingeridos, percepção de vazamento de gases e de incêndios, sua avaliação clínica ainda não se encontra padronizada no Brasil. O Teste de Identificação do Olfato da Universidade da Pensilvânia (UPSIT) é um teste mundialmente utilizado e considerado por muitos como o padrão-ouro da avaliação olfatória. Originalmente em inglês, já foi traduzido para mais de 12 línguas. Esse trabalho se propôs a validar de forma inédita o UPSIT para outra cultura. O UPSIT versão em português foi validado para a população brasileira e tabelas normativas foram elaboradas para comparação do escore obtido segundo o sexo e idade do indivíduo. Secundariamente, procurou-se os fatores preditores de um melhor escore no teste. CASUÍSTICA E MÉTODOS: Estudo transversal realizado de dezembro de 2011 a agosto de 2012. A amostra utilizada foi não-probabilística por quotas e constituída por indivíduos presentes em uma instituição de atendimento público (Poupatempo São Paulo), de forma consecutiva, sem queixas olfatórias no dia do exame. Foi determinada a quota de 60 brasileiros(as) em cada faixa etária de cada sexo, a saber: 20-24, 25-30, 31-34, 35-40, 41-44, 45-50, 50-54, 55-59, 60-64, 65-69, 70-74, 75-79 e >= 80 anos. Após responderem questionário referente a dados demográficos e critérios de inclusão e exclusão do estudo, fizeram o UPSIT 782 indivíduos do sexo masculino e 796 do sexo feminino. Nos pacientes com idade igual ou superior a 65 anos foi realizado o Mini Exame do Estado Mental e se excluíram aqueles pacientes com escore inferior a 24 pontos pela possibilidade de quadro demencial. A versão do UPSIT aplicada nesse estudo foi resultado de dois estudos prévios para melhorar a aplicabilidade desse teste para a população brasileira. RESULTADOS: 1820 voluntários participaram do estudo, 1578 foram incluídos nas tabelas normativas. 242 foram excluídos no dia da entrevista por estarem com infecção das vias aéreas superiores, terem história de trauma crânio-encefálico, queixa de perda de olfato ou paladar e um escore menor de 24 no Mini Exame do Estado Mental. Verificou-se que entre os 1578 indivíduos analisados, o escore de UPSIT variou de 9 a 40, obtendo-se escore médio de 32,1 (desvio padrão: 5,3) e escore mediano igual a 33. Pela análise univariada (p < 0,01) e multivariada - regressão linear múltipla- (p < 0,05), observou-se que a idade, sexo, número de anos de estudo e renda mensal da família influíram no escore do teste. CONCLUSÕES: O UPSIT está agora validado para utilização na população brasileira. Disponibilizou-se tabelas normativas para avaliação olfatória e um modo rápido de obtê-las. Fatores de correção são necessários para uma perfeita equivalência entre as normas de todos os continentes, utilizando como padrão-ouro as normas do país onde a versão original do teste foi desenvolvida. Pior status econômico e educacional interferem negativamente na performance olfatória / INTRODUCTION: Despite the fundamental importance of olfaction to assess the flavors of food, perception of gas leakage and fire, its clinical evaluation is not yet standardized in Brazil. The University of Pennsylvania Smell Identification Test of the (UPSIT) is a test used worldwide and considered by many as the gold standard of olfactory assessment. Originally in English, it has been translated into more than 12 languages. This study aimed to validate the UPSIT for another culture in a novel form. The portuguese version of UPSIT Portuguese version was validated for the Brazilian population and normative tables were prepared to compare the score obtained by sex and age of the individual. Secondarily, we sought the predictors of a better score on the test. PATIENTS AND METHODS: Cross-sectional study conducted from December 2011 to August 2012. The sample used was a non-probabilistic by quotas and consisted of individuals present in a public service institution (Poupatempo São Paulo), consecutively, without olfactory complaints on exam day. We determined the quota of 60 Brazilians in each age group for each sex, as follows: 20-24, 25-30, 31-34, 35-40, 41-44, 45-50, 50-54, 55 -59, 60-64, 65-69, 70-74, 75-79 and >= 80 years. After answering a questionnaire about demographics and inclusion and exclusion criteria of the study, 782 males and 796 females did the UPSIT. In patients aged over 65 years was held the Mini Mental State Examination and excluded those patients with a score less than 24 points for the possibility of dementia. The version of the UPSIT applied in this study was the result of two previous studies to enhance the applicability of this test for the Brazilian population. RESULTS: 1820 volunteers participated in the study, 1578 were included in the normative tables. 242 were excluded on the day of the interview for being with upper airway infection, having an history of head trauma, complaining of smell or taste losses and a score below 24 on the Mini Mental State Examination. It was found that among the 1578 subjects analyzed, the UPSIT scores ranged from 9 to 40, yielding a mean score of 32.1 (SD: 5.3) and a median 33. By univariate analysis (p < 0.01) and multivariate analysis - multiple linear regression-(p < 0.05), it was observed that the age, sex, years of schooling and family monthly income influenced the test scores. CONCLUSIONS: UPSIT is now validated for use in the Brazilian population. Normative tables for olfactory assessment and a fast way to obtain them were demonstrated. Correction factors are needed for a perfect equivalence between norms of all continents, using as gold standard norms of the country where the original version of the test was developed. Worse economic and educational status interfered negatively in olfactory performance

INTRODUÇÃO: Apesar da fundamental importância da olfação para avaliação dos sabores dos alimentos ingeridos, percepção de vazamento de gases e de incêndios, sua avaliação clínica ainda não se encontra padronizada no Brasil. O Teste de Identificação do Olfato da Universidade da Pensilvânia (UPSIT) é um teste mundialmente utilizado e considerado por muitos como o padrão-ouro da avaliação olfatória. Originalmente em inglês, já foi traduzido para mais de 12 línguas. Esse trabalho se propôs a validar de forma inédita o UPSIT para outra cultura. O UPSIT versão em português foi validado para a população brasileira e tabelas normativas foram elaboradas para comparação do escore obtido segundo o sexo e idade do indivíduo. Secundariamente, procurou-se os fatores preditores de um melhor escore no teste. CASUÍSTICA E MÉTODOS: Estudo transversal realizado de dezembro de 2011 a agosto de 2012. A amostra utilizada foi não-probabilística por quotas e constituída por indivíduos presentes em uma instituição de atendimento público (Poupatempo São Paulo), de forma consecutiva, sem queixas olfatórias no dia do exame. Foi determinada a quota de 60 brasileiros(as) em cada faixa etária de cada sexo, a saber: 20-24, 25-30, 31-34, 35-40, 41-44, 45-50, 50-54, 55-59, 60-64, 65-69, 70-74, 75-79 e >= 80 anos. Após responderem questionário referente a dados demográficos e critérios de inclusão e exclusão do estudo, fizeram o UPSIT 782 indivíduos do sexo masculino e 796 do sexo feminino. Nos pacientes com idade igual ou superior a 65 anos foi realizado o Mini Exame do Estado Mental e se excluíram aqueles pacientes com escore inferior a 24 pontos pela possibilidade de quadro demencial. A versão do UPSIT aplicada nesse estudo foi resultado de dois estudos prévios para melhorar a aplicabilidade desse teste para a população brasileira. RESULTADOS: 1820 voluntários participaram do estudo, 1578 foram incluídos nas tabelas normativas. 242 foram excluídos no dia da entrevista por estarem com infecção das vias aéreas superiores, terem história de trauma crânio-encefálico, queixa de perda de olfato ou paladar e um escore menor de 24 no Mini Exame do Estado Mental. Verificou-se que entre os 1578 indivíduos analisados, o escore de UPSIT variou de 9 a 40, obtendo-se escore médio de 32,1 (desvio padrão: 5,3) e escore mediano igual a 33. Pela análise univariada (p < 0,01) e multivariada - regressão linear múltipla- (p < 0,05), observou-se que a idade, sexo, número de anos de estudo e renda mensal da família influíram no escore do teste. CONCLUSÕES: O UPSIT está agora validado para utilização na população brasileira. Disponibilizou-se tabelas normativas para avaliação olfatória e um modo rápido de obtê-las. Fatores de correção são necessários para uma perfeita equivalência entre as normas de todos os continentes, utilizando como padrão-ouro as normas do país onde a versão original do teste foi desenvolvida. Pior status econômico e educacional interferem negativamente na performance olfatória / INTRODUCTION: Despite the fundamental importance of olfaction to assess the flavors of food, perception of gas leakage and fire, its clinical evaluation is not yet standardized in Brazil. The University of Pennsylvania Smell Identification Test of the (UPSIT) is a test used worldwide and considered by many as the gold standard of olfactory assessment. Originally in English, it has been translated into more than 12 languages. This study aimed to validate the UPSIT for another culture in a novel form. The portuguese version of UPSIT Portuguese version was validated for the Brazilian population and normative tables were prepared to compare the score obtained by sex and age of the individual. Secondarily, we sought the predictors of a better score on the test. PATIENTS AND METHODS: Cross-sectional study conducted from December 2011 to August 2012. The sample used was a non-probabilistic by quotas and consisted of individuals present in a public service institution (Poupatempo São Paulo), consecutively, without olfactory complaints on exam day. We determined the quota of 60 Brazilians in each age group for each sex, as follows: 20-24, 25-30, 31-34, 35-40, 41-44, 45-50, 50-54, 55 -59, 60-64, 65-69, 70-74, 75-79 and >= 80 years. After answering a questionnaire about demographics and inclusion and exclusion criteria of the study, 782 males and 796 females did the UPSIT. In patients aged over 65 years was held the Mini Mental State Examination and excluded those patients with a score less than 24 points for the possibility of dementia. The version of the UPSIT applied in this study was the result of two previous studies to enhance the applicability of this test for the Brazilian population. RESULTS: 1820 volunteers participated in the study, 1578 were included in the normative tables. 242 were excluded on the day of the interview for being with upper airway infection, having an history of head trauma, complaining of smell or taste losses and a score below 24 on the Mini Mental State Examination. It was found that among the 1578 subjects analyzed, the UPSIT scores ranged from 9 to 40, yielding a mean score of 32.1 (SD: 5.3) and a median 33. By univariate analysis (p < 0.01) and multivariate analysis - multiple linear regression-(p < 0.05), it was observed that the age, sex, years of schooling and family monthly income influenced the test scores. CONCLUSIONS: UPSIT is now validated for use in the Brazilian population. Normative tables for olfactory assessment and a fast way to obtain them were demonstrated. Correction factors are needed for a perfect equivalence between norms of all continents, using as gold standard norms of the country where the original version of the test was developed. Worse economic and educational status interfered negatively in olfactory performance

Les informations olfactives sont connues pour leur capacité à induire des comportements moteurs spécifiques. En dépit de nombreuses observations comportementales chez les vertébrés, on ne connaît toujours pas les mécanismes et les voies nerveuses qui sous-tendent ces phénomènes de transformation olfacto-locomotrices. Chez la lamproie, des travaux récents ont permis de décrire cette voie, et les mécanismes responsables de la transformation des entrées olfactives en activité locomotrice (Derjean et al., 2010). Cette voie prend origine dans la partie médiane du bulbe olfactif, et envoie des projections vers le tubercule postérieur, une région qui se trouve dans le diencéphale. De là, les neurones projettent directement vers la Région Locomotrice Mésencéphalique, connue pour envoyer des connexions vers les neurones réticulospinaux, et activer la locomotion. L’objectif de cette étude était d’établir si l’ensemble des neurones réticulospinaux répond aux stimulations olfactives. Pour ce faire, nous avons utilisé sur une préparation de cerveau isolé de lamproie des techniques d’électrophysiologie et d’imagerie calcique. La stimulation électrique des nerfs olfactifs, de la région médiane du bulbe olfactif ou du tubercule postérieur a provoqué une activation de toutes les cellules réticulospinales qui se retrouvent dans les quatre noyaux réticulaires (ARRN : Noyau Réticulaire Rhombencéphalique Antérieur; MRN : Noyau Réticulaire Mésencéphalique; MRRN : Noyau Réticulaire Rhombencéphalique Moyen; PRRN : Noyau Réticulaire Rhombencéphalique Postérieur). Seule la partie médiane du bulbe olfactif est impliquée dans le passage de l’information olfactive vers les neurones réticulospinaux. Nous avons aussi découvert que le blocage des récepteurs GABAergiques dans la partie médiane du bulbe olfactif augmentait les réponses olfactives de façon considérable dans les cellules réticulospinales. Nous avons montré ainsi qu’il existe un tonus inhibiteur impliqué dans la dépression modulatrice de la voie olfacto-locomotrice. Ce travail a permis de montrer que la stimulation des afférences sensorielles olfactives active simultanément l’ensemble des populations de neurones réticulospinaux qui commandent la locomotion. De plus, il existerait un tonus inhibiteur GABAergique, au niveau de la partie médiane du bulbe olfactif, responsable d’une dépression modulatrice dans la voie olfacto-locomotrice. / Olfactory inputs are known for their ability to induce specific motor behaviors. Despite numerous behavioral observations in vertebrates, the mechanisms and the neural pathways underlying the olfactory-locomotor transformation are still unknown. In lamprey, recent studies have described this pathway and the mechanism underlying the transformation of olfactory input into a locomotor activity (Derjean et al., 2010). This pathway originates in the medial part of the olfactory bulb, sends projections to the posterior tuberculum, a diencephalic region. From there, the neurons project directly to the mesencephalic locomotor region that is known to send projections to the reticulospinal neurons to activate locomotion. Using lamprey brain preparation, electrophysiology and calcium imaging, the aim of this study was to establish whether all reticulospinal neurons respond to olfactory stimuli. Electrical stimulation of the olfactory nerves, the medial part of the olfactory bulb or the posterior tuberculum activates all reticulospinal cells in the four reticular nuclei (ARRN: Anterior rhombencephalic reticular nucleus; MRN: middle mesencephalic reticular nucleus; MRRN: middle rhombencephalic reticular nucleus; PRRN: posterior rhombencephalic reticular nucleus). The medial part of the olfactory bulb is the only region that is implicated in transmitting the olfactory information to reticulospinal neurons. We also discovered that when blocking the GABAergic receptors in the medial part of the olfactory bulb, the reticulospinal neurons have a stronger response to olfactory stimulation. Thus we showed that a tonic inhibition is involved in the modulating depression of the olfacto-locomotor pathway. Altogether, this work shows that stimulation of the olfactory sensory inputs activates simultaneously the entire population of reticulospinal neurons that control locomotion. In addition, there is a GABAergic tonic inhibition at the level of the medial part of the olfactory bulb that causes a modulating depression in the olfacto-locomotor pathway.