Long-term memories turn labile with reactivation and undergo a re-stabilization process, termed reconsolidation, involving molecular changes that allow updating of an existing memory trace. Such molecular changes may involve the activation of kinases and expression of proteins related to the increase of synaptic plasticity and memory formation. A kinase reported to have a role in a variety of memory tasks is the extracellular signal-regulated kinase 1/2 (ERK1/2). The downstream activation of ERK targets other regulatory enzymes, transcription factors and cytoskeletal proteins, which allow structural changes in the neuron due to protein synthesis up-regulation. Among the proteins up-regulated by ERK activity is the activity-regulated cytoskeleton-associated protein (ARC), an immediate early gene related to synaptic plasticity. The phase-dependent roles of ERK and ARC have not been examined as part of the molecular mechanisms triggered after a learning experience. In this study I used conditioned taste aversion (CTA) as the learning paradigm and investigated the expression of pERK and ARC in brain regions critical for taste information processing such as the insular cortex and the amygdala. A differential pattern of protein expression was observed in the insular cortex (IC) two hours after taste memory acquisition: pERK activity increased in the aversively conditioned group while ARC increased in the group that received only the novel taste. The central amygdala (CeA) showed a significant increase in pERK, but not ARC activity after CTA training. Immunoblotting experiments performed after memory retrieval in the appetitive group show that pERK continues to signal aversive taste to the IC with ARC exhibiting heightened expression an hour later. An increase in ARC expression 30 minutes after reactivation of the aversive taste was seen in the basolateral amygdala and the CeA exhibited a similar increase at 60 and 90 minutes. Local infusion of ARC antisense oligonucleotides within the IC interfered with the consolidation of safe taste memories, but not with their acquisition. Trace update experiments showed that ARC influences the memory switch from aversive to safe, but not the reverse. Our results indicate that ARC plays a critical role in consolidation and updating of safe taste memories, and the ARC signaling could possibly elicit ERK activation.

O objetivo desta dissertação é compreender o conceito de padrão moral na filosofia de David Hume. Qual sua importância? O padrão moral regula os juízos morais. Todos os juízos de valor dependem do gosto e de sentimentos de prazer ou desagrado. Mas o que é o gosto? Quais objetos ele julga? Como ele forma juízos? Em moral, o objeto do gosto é o caráter pessoal. O caráter virtuoso causa prazer, o vicioso causa desgosto. Sentimos prazer com um caráter virtuoso porque ele contribui para a felicidade da espécie humana. Sentimos prazer com a felicidade de nossa espécie por causa de um instinto denominado benevolência. Todos nós temos esse instinto, existe uma natureza humana. Alguns juízos de gosto são defectivos, mas o refinamento corrige-os. O padrão moral é instituído pelo refinado gosto de indivíduos que contemplaram a natureza humana. Eles são chamados de moralistas. Moralistas humanizam a humanidade. São essas as principais teses examinadas aqui. / This dissertation aims to comprehend the concept of moral standard in David Humes philosophy. Why is it important? The moral standard regulates moral judgments. All value judgments depend on taste and on sentiments of pleasure or dislike. But what is taste? What objects does it judge? How does it make judgments? The object of taste on morals is personal character. The virtuous character causes pleasure, the vicious character causes disgust. We feel pleasure with a virtuous character, for he promotes the happiness of the human species. We feel pleasure with the happiness of our species because of an instinct denominated benevolence. We all have this instinct, there is a human nature. Some judgments of taste are defective, but refinement corrects them. The moral standard is instituted by the refined taste of individuals who contemplated human nature. They are called moralists. Moralists humanize humanity. These are the principal theses here examined.

La composition chimique des aliments est perçue par les bourgeons du goût et transmise au cerveau postérieur par des nerfs viscérosensoriels particuliers, les nerfs du goût. L’intégrité de ces nerfs est essentielle au maintien des bourgeons du goût chez les animaux adultes. Cependant, leur rôle dans l’ontogénie des bourgeons, chez l’embryon et aux premiers stades postnataux, est controversé and reste non résolu. Dans cette étude, j’ai établi de façon définitive que la formation embryonnaire des bourgeons du goût dépend des nerfs gustatifs chez la souris, unifiant ainsi les mécanismes de maintien/régénération et d’ontogénie de ces organes. En parallèle, j’ai réexaminé la possibilité (jusque-là exclue par d’autres auteurs) d’un rôle du facteur de transcription Foxg1 dans la formation des ganglions sensoriels épibranchiaux. J’ai découvert que Foxg1 est un déterminant des neurones gustatifs dans le ganglion géniculé. Ce nouveau rôle, de pair avec ceux décrits précédemment dans l’épithélium olfactif, la placode otique et la rétine, révèle une cohérence physiologique remarquable des fonctions de Foxg1 (en dehors de son rôle bien établi dans le cortex) en tant que facteur de transcription maître des neurones impliqués dans les « sens spéciaux » : vision, ouïe, odorat et goût. / Taste information is received by taste buds and transmitted to the hindbrain by special visceral sensory nerves, the taste nerves. The integrity of taste nerves is essential for the maintenance of taste buds in adult animals. However, a role for taste nerves in the ontogeny of taste buds, in the embryo and at early postnatal stages, has been controversial and is still unresolved. In this study, I establish in a definitive manner that embryonic taste bud formation is nerve-dependent in mouse, thus unifying mechanistically the maintenance/regeneration and ontogeny of these organs. Parallel to this work, I re-examined the possibility (previously excluded by other authors) of a role for the transcription factor Foxg1 in epibranchial ganglion formation. I find that Foxg1 is essential for the differentiation of gustatory neurons in the geniculate ganglion. This novel role, together with previously described ones in the olfactory epithelium, otic placode and retina, unveils a striking physiological coherence of the functions of Foxg1 (outside its well established one in the cortex), as a master transcription factor for neurons involved in “special senses”: vision, hearing, smell and taste.

In addition to the contribution of lipids to food texture and aroma, the effect of lipids on taste perception is now commonly studied. It has been found that lipids may affect taste perception through lipid composition (i.e., cis-polyunsaturated fatty acids). This study assessed the effect of lipid composition on the recognition thresholds of the basic tastes (i.e., sour, umami, bitter, salty, sweet) in emulsion model systems as well as taste intensities perceived at low suprathreshold concentrations. Taste thresholds and intensities in corresponding aqueous systems were determined for comparison. To evaluate the effect of lipid chemical composition on tastant detection, 20% oil emulsions were formulated with either anhydrous milk fat, soybean oil, or a blend comprised of a 1:1 ratio (by weight) of milk fat and soybean oil. Prior to taste testing, emulsions were deemed to have the necessary physicochemical characteristics (i.e., stability, pH, droplet size, viscosity) for use in taste experiments. Thresholds were determined according to the ASTM forced-choice ascending concentration series method using 11 trained panelists. Taste intensities were rated on a numerical scale of zero to 15 by 10 trained panelists. As expected, aqueous thresholds were generally lower than those of respective emulsions; however, these differences were not always found to be significant. Though lipid composition affected emulsion thresholds slightly for all tastes except bitter, a significant relationship between thresholds and fat composition was not established. Taste intensity appears to increase proportionally to increases in tastant concentration at suprathreshold concentrations near recognition threshold. Some results from taste intensity experiments indicate that fatty acid composition may be influencing results, but the implications are unclear based upon these experiments. These results suggest that the role of lipids in taste perception is more complex than simply correlating with an increase in polyunsaturated fatty acids in general.

No description available.

A presente pesquisa se concentra na recuperação da acepção setecentista dos conceitos de estilo e de gosto na música. Com base em fontes originais do séc. XVIII, mostra como a idéia de gosto veio a se associar à de estilo no decorrer do século XVIII, passando a constituir a base de termos como gostos reunidos e estilo galante, comumente relacionados à música de Georg Philipp Telemann (1681-1767). Este estudo aborda os estilos e gostos adotados por Telemann a partir de uma perspectiva histórica e, para tanto, utiliza as retóricas clássicas, nas quais se apoiaram os autores setecentistas; os tratados sobre gosto dos séc. XVII e XVIII; as poéticas musicais setecentistas; e as autobiografias de Telemann (de 1718 e 1740). Deste modo, propomos o estudo de ambos os conceitos não apenas a partir de sua perspectiva técnica ou nacional, mas recuperando sua função dentro do contexto da elocutio retórica, envolvendo a idéia de decoro. Nas fontes setecentistas, o uso destes termos se relaciona com os sistemas de adequação entre as diferentes maneiras de escrita em relação à ocasião e ao gosto nacional, ambos regulados pelo decoro. Desta forma, estes conceitos constituem aspectos de uma concepção musical única, que pode ser melhor compreendida a partir da perspectiva dupla do gosto e do estilo. No séc. XVIII, o gosto regulava as maneiras de compor, formando estilos próprios de um determinado grupo, país, ou auctoritas. Os dois principais parâmetros de gosto normativos do período são a música francesa e a italiana. Deste modo, a partir da imitação e do estudo dos modelos estrangeiros formou-se a prática denominada gostos reunidos - mencionada nos escritos setecentistas alemães como gemischten Goût, vermischter Geschmack e Gosto Alemão. Deste processo de imitação, onde tomar algo como modelo não se refere a uma cópia do discurso, mas sim à aprendizagem e exercitação de como tratar tecnicamente um material de origens diversas a fim de gerar algo novo, surge um novo gênero, denominado por Telemann e seus contemporâneos como Concert en Ouverture, ou Concertouverture. / This research is focused on recovering the seventeenth-century sense of the concepts style and taste in music. Based on original works from the eighteenth century, presents the process of association between the ideas of taste and style during the eighteenth century, becoming the basis of terms as mixed tastes and gallant style, often used on descriptions of Georg Philipp Telemann (1681-1767) music. This study analyses the styles and tastes used by Telemann from a historical approach, using the classical rethoric in which the seventeenth-century authors based their writings; treatises about taste from the seventeenth and eighteenth century period; musical poetics from the seventeenth century and Telemann´s autobiographies (from 1718 an 1740). This work proposed the study of both concepts not only from the technical or national perspectives, but recovering its place on the rhetoric context of elocutio tied to the notion of decorum. The use of the previous terms in the works from the seventeenth century relates them to the suitability between different ways of composition for each circumstance and national taste, both ruled by decorum. Hence, these concepts are part of an unique musical notion, that can be better understood from the parallel perspectives of taste and style. In eighteenth century, taste ruled composition forms, generating peculiar styles from certain groups, countries and auctoritas. The two main normative parameters of taste in the period were French and Italian music. Thus, from the study and imitation of foreign styles, the practice known as mixed tastes was shaped - it was mentioned in the seventeenth-century German writings as gemischten Goût, vermischter Geschmack and German taste. From this imitation process, where following something as example was not understood as copying the content, but learning and practising the process of working on materials from various sources with the purpose of building something new, a new genre arises. It\'s called by Telemann and his contemporaries Concert en Ouverture, or Concertouverture.

L'obésité constitue l'un des principaux problèmes de santé publique en ce début du 21ème siècle. Sa prévalence augmente régulièrement, en particulier chez les enfants. Ce constat n'est pas anodin car l'obésité est généralement associée à diverses pathologies graves (diabète de type 2, hypertension et cancer,…). Ainsi, des investigations sur les mécanismes impliqués dans la perception gustative des lipides alimentaires pourraient éclairer leurs rôles dans l’incidence de l’obésité.Plusieurs études ont démontré le rôle des endocannabinoïdes et des aliments amers dans l’obésité. Ainsi, nous avons étudié l’interaction (cross-talk) des récepteurs cannabinoïdes et du goût amer avec le goût lipidique. Cette thèse comporte ainsi deux volets : les récepteurs cannabinoïdes (CB1R), le goût amer et leurs interactions avec les récepteurs lipidiques.Dans la première partie, nous avons étudié le rôle régulateur de CB1R. Dans la présente étude, des tests comportementaux sur des souris CB1R-/- et des souris de type sauvage (WT) ont montré que l'invalidation du gène Cb1r était associée à une faible préférence pour les solutions contenant de l'huile de colza ou un acide gras à longue chaîne (AGLC) tel que l’acide linoléique (LA). L'administration de rimonabant, un agoniste-inverse de CB1R, chez la souris a également entraîné une faible préférence pour les acides gras alimentaires. Aucune différence dans l'expression des protéines CD36 et GPR120 n'a été observée dans les cellules des papilles gustatives des souris WT et CB1R-/-. La signalisation calcique via CD36 dans les cellules des papilles gustatives des souris CB1R-/- diminue de façon significative par rapport à celle observée dans les cellules gustatives des souris WT. Les cellules des papilles gustatives des souris CB1R-/- présentent également une diminution significative de l'ARNm de Pro-glucagon et de Glp-1r et un faible niveau basal de GLP-1. Nous rapportons que CB1R est impliqué dans la perception du goût du gras via la signalisation calcique et la sécrétion de GLP-1.Dans la seconde partie, nous avons d’abord caractérisé le phénotype de cellules fongiformes humaines (HTC-8). En effet, le projet de ma thèse comprend la caractérisation à l’échelle moléculaire des récepteurs amers et lipidiques et leur cross-talk dans ces cellules (collaboration BRAIN, Allemagne). Nous avons démontré que les cellules HTC-8 expriment PLCβ2 et l’α-gustducin à l’échelle des ARNm et des protéines. Elles expriment également TAS2R16 et TAS2R38 et ces mêmes cellules co-expriment CD36 et GPR120. Puis, nous avons étudié la signalisation via ces récepteurs en utilisant l’acide linoléique, un agoniste de CD36 et GPR120, la sinigrin, agoniste de TAS2R16 et TAS2R38, la salicin, agoniste du récepteur TAS2R16 et le phénylthiocarbamide, agoniste du récepteur TAS2R38. De plus, les études du signal calcique ont démontré que la signalisation en aval du goût gras partage une voie commune avec la signalisation en aval du goût amer, mettant en évidence un cross-talk entre ces deux modalités gustatives.Bien que nous ayons montré le cross-talk entre les modalités gustatives amère et lipidique, il nous reste à étudier ces phénomènes à l’échelle de l’organisme. Ces résultats, d’ores et déjà, montrent que le goût amer et le récepteur cannabinoïde-1 sont liés à la sensibilité au goût du gras et doivent être pris en compte pour la gestion de l'obésité. / Obesity is one of the major public health problems at the beginning of the 21st century. Its prevalence is increasing steadily, especially among children. This observation is not insignificant because obesity is generally associated with various serious pathologies (type 2 diabetes, hypertension and cancer, etc.). Thus, investigations into the mechanisms involved in the taste perception of dietary lipids could shed light on their roles in the incidence of obesity.Several studies have demonstrated the role of endocannabinoids and bitter foods in obesity. Thus, we studied the cross-talk of cannabinoid receptors and bitter taste with lipid taste. This thesis has two components: cannabinoid receptors (CB1R), bitter taste and their interactions with lipid receptors.In the first part, we studied the regulatory role of CB1R. In the present study, behavioral tests on CB1R-/- mice and wild-type (WT) mice showed that the invalidation of the Cb1r gene was associated with a low preference for solutions containing rapeseed oil or a long chain fatty acid (LCFA) such as linoleic acid (LA). Administration of rimonabant, a CB1R inverse agonist, in mice also resulted in a low preference for dietary fatty acids. No differences in the expression of CD36 and GPR120 proteins were observed in the taste buds cells of the WT and CB1R-/- mice. Calcium signaling via CD36 in the taste bud cells of CB1R-/- mice decreased significantly compared with those observed in the taste cells of WT mice. The taste bud cells of CB1R-/- mice also show a significant decrease in Pro-glucagon and Glp-1r mRNA and a low basal level of GLP-1. We report that CB1R is involved in the perception of fat taste via calcium signaling and secretion of GLP-1.In the second part, we first characterized the phenotype of human fungiform cells (HTC-8). Indeed, the project of my thesis includes the characterization on the molecular scale of bitter and lipid receptors and their cross-talk in these cells (collaboration BRAIN, Germany). We have demonstrated that HTC-8 cells express PLCβ2 and α-gustducin at the mRNA and protein level. They also express TAS2R16 and TAS2R38 and these same cells co-express CD36 and GPR120. Then, we studied signaling via these receptors using linoleic acid, a CD36 and GPR120 agonist, sinigrin, TAS2R16 agonist and TAS2R38, salicin, TAS2R16 receptor agonist, and phenylthiocarbamide, TAS2R38 receptor agonist. In addition, calcium signal studies have shown that downstream fatty signaling shares a common path with downstream bitter taste signaling, highlighting a cross-talk between these two taste modalities.Although we have shown the cross-talk between bitter and lipid taste modalities, we still have to study these phenomena at the level of the organism. These results, already, show that the bitter taste and the cannabinoid-1 receptor are related to the taste sensitivity of fat and must be taken into account for the management of obesity

A presente pesquisa se concentra na recuperação da acepção setecentista dos conceitos de estilo e de gosto na música. Com base em fontes originais do séc. XVIII, mostra como a idéia de gosto veio a se associar à de estilo no decorrer do século XVIII, passando a constituir a base de termos como gostos reunidos e estilo galante, comumente relacionados à música de Georg Philipp Telemann (1681-1767). Este estudo aborda os estilos e gostos adotados por Telemann a partir de uma perspectiva histórica e, para tanto, utiliza as retóricas clássicas, nas quais se apoiaram os autores setecentistas; os tratados sobre gosto dos séc. XVII e XVIII; as poéticas musicais setecentistas; e as autobiografias de Telemann (de 1718 e 1740). Deste modo, propomos o estudo de ambos os conceitos não apenas a partir de sua perspectiva técnica ou nacional, mas recuperando sua função dentro do contexto da elocutio retórica, envolvendo a idéia de decoro. Nas fontes setecentistas, o uso destes termos se relaciona com os sistemas de adequação entre as diferentes maneiras de escrita em relação à ocasião e ao gosto nacional, ambos regulados pelo decoro. Desta forma, estes conceitos constituem aspectos de uma concepção musical única, que pode ser melhor compreendida a partir da perspectiva dupla do gosto e do estilo. No séc. XVIII, o gosto regulava as maneiras de compor, formando estilos próprios de um determinado grupo, país, ou auctoritas. Os dois principais parâmetros de gosto normativos do período são a música francesa e a italiana. Deste modo, a partir da imitação e do estudo dos modelos estrangeiros formou-se a prática denominada gostos reunidos - mencionada nos escritos setecentistas alemães como gemischten Goût, vermischter Geschmack e Gosto Alemão. Deste processo de imitação, onde tomar algo como modelo não se refere a uma cópia do discurso, mas sim à aprendizagem e exercitação de como tratar tecnicamente um material de origens diversas a fim de gerar algo novo, surge um novo gênero, denominado por Telemann e seus contemporâneos como Concert en Ouverture, ou Concertouverture. / This research is focused on recovering the seventeenth-century sense of the concepts style and taste in music. Based on original works from the eighteenth century, presents the process of association between the ideas of taste and style during the eighteenth century, becoming the basis of terms as mixed tastes and gallant style, often used on descriptions of Georg Philipp Telemann (1681-1767) music. This study analyses the styles and tastes used by Telemann from a historical approach, using the classical rethoric in which the seventeenth-century authors based their writings; treatises about taste from the seventeenth and eighteenth century period; musical poetics from the seventeenth century and Telemann´s autobiographies (from 1718 an 1740). This work proposed the study of both concepts not only from the technical or national perspectives, but recovering its place on the rhetoric context of elocutio tied to the notion of decorum. The use of the previous terms in the works from the seventeenth century relates them to the suitability between different ways of composition for each circumstance and national taste, both ruled by decorum. Hence, these concepts are part of an unique musical notion, that can be better understood from the parallel perspectives of taste and style. In eighteenth century, taste ruled composition forms, generating peculiar styles from certain groups, countries and auctoritas. The two main normative parameters of taste in the period were French and Italian music. Thus, from the study and imitation of foreign styles, the practice known as mixed tastes was shaped - it was mentioned in the seventeenth-century German writings as gemischten Goût, vermischter Geschmack and German taste. From this imitation process, where following something as example was not understood as copying the content, but learning and practising the process of working on materials from various sources with the purpose of building something new, a new genre arises. It\'s called by Telemann and his contemporaries Concert en Ouverture, or Concertouverture.

Individuella smakupplevelser varierar stort och är delvis beroende av hur väl och intensivt individen kan urskilja grundsmaker. Jämfört med vuxna uppvisar barn en högre preferens för sött och starkare aversion mot bittert. Syftet med denna studie var att undersöka 4-6-åriga förskolebarns förmåga att identifiera grundsmaker i livsmedel före och efter träning med grundsmaklösningar. Även barnens förmåga att verbalisera smakupplevelser innan grundsmakträning undersöktes. Studien genomfördes på en förskola, totalt elva barn deltog i studien som bestod av fyra moment. En gruppdiskussion om (grund)smaker, provsmakning av tio olika livsmedel med fortsatt samtal om vad dessa smakade. Tredje momentet var träning med grundsmaklösningar där barnen fick öva på att känna igen sött, surt, salt, bittert och umami. Sista momentet var ett grundsmaktest där barnen fick svara vilka grundsmaker de kunde identifiera i varje livsmedel. Resultaten visade på en signifikant skillnad förmåga att uppfatta salt jämfört med övriga grundsmaker, samt en markant ökad förmåga att både identifiera och verbalisera samtliga grundsmaker i livsmedel efter grundsmakträning. Från att ha benämnt ”gott” och ”äckligt” som smaker kunde barnen efter träning i större utsträckning sätta ord på och identifiera flera olika grundsmaker i livsmedlen de smakade. En kort grundsmakträning är en enkel metod som kan bidra till att få små barn att inta ett positivt, nyfiket förhållningssätt till nya smaker och mat i allmänhet. / Individual experiences of taste differs greatly and is partially due to both the ability to detect basic taste and the intensity at which it is interpreted. Compared to grown-ups, children tend to show a higher preference toward sweet and a greater aversion towards bitter. The purpose of this study was to examine 4-6-year old pre-school children’s ability to identify basic tastes in food before and after training with basic taste solutions. The children’s ability to articulate their taste experiences were also studied before basic taste training. The research were conducted at a single pre-school, eleven children participated in the study which involved four different parts. A group discussion about (basic) tastes, testing of ten different foods accompanied by continued conversations about what the food tasted like. The third part was training with basic taste solutions where the children got to practice recognizing sweet, sour, salty, bitter and umami. The last part were a basic taste test in which the children were asked to answer what basic tastes they could identify in each food. The results showed a significant difference in the children’s ability to identify salty tastes compared to other basic tastes, also a notably improved ability to detect and articulate all basic tastes after basic taste training. The children went from naming “tasty” and “disgusting” as tastes, to being able to put words on, and identify, many of the basic tastes in each food. A short training session with basic tastes is a simple method which can benefit young children by contributing to a more positive and curious approach towards new flavours and food in general.

Taste buds are chemosensory endorgans embedded in the oral epithelium composed of cells that undergo continuous replacement. Mature taste cells live on average 10-14 days and are replaced by new cells when they die. However, the mechanism by which taste cells are produced and integrated into the taste bud as mature taste cells remains unknown. Previous studies approached this issue from either cell cycle gene expression properties or lineage tracing of precursor cells. In our study, we apply a new fate mapping technique that combines these two ideas. This technique, Mosaic Analysis with Double Markers, allows for simultaneous gene knockout and subsequent tracking of single cells. This allows us to study the potency of precursor cells supplying the taste bud while analyzing how gene function regulates the maturation pathway these taste cells take. The following experiments illustrate the initial phase of this investigation.