Winterreise et Die sieben Todsünden : un regard sur l’aliénation du sujet moderne

La version intégrale de cette thèse est disponible uniquement pour consultation individuelle à la Bibliothèque de musique de l’Université de Montréal (www.bib.umontreal.ca/MU).Cause principale du malaise moderne, l’aliénation désigne l’état de l’être humain qui est pris entre ce qu’il est et ce qu’il devrait être. Ma thèse démontre que la représentation de cette déficience ontologique dans l’art vocal connaît des modalités subjective et objective. Séduit par une oeuvre de la première modalité, l’auditeur en subit l’ensorcellement et sympathise avec le protagoniste aliéné. Se heurtant à la seconde modalité, le spectateur se trouve aux prises avec une oeuvre qui vise à empêcher tout effet d’identification émotif avec le personnage principal. Tout en prenant position par rapport aux traditions herméneutique et critique, je cherche à approfondir la question de l’aliénation dans la musique de la modernité germanique (comprise dans les limites des XIXe et XXe siècles), et ce, sous ses différentes formes. Le Winterreise de Franz Schubert (et Wilhelm Müller) et le ballet chanté, Die sieben Todsünden, de Kurt Weill (et Bertolt Brecht) exemplifient les différentes modalités de l’aliénation, subjective et objective, respectivement. Ma thèse aborde le concept d’aliénation à partir de différentes perpectives : le premier chapitre en retrace le développement dans l’histoire des idées (philosophie, théologie, esthétique, sciences sociales, psychanalyse); les chapitres 2, 3 et 5 étudient l’expression de ses différentes modalités en examinant la genèse et la réception du Winterreise et de Die sieben Todsünden; les chapitres 4 et 6 offrent des analyses approfondies de chaque oeuvre en rapport avec ces modalités. Dans le Winterreise, la présence du double (le joueur de vielle), la narration à la première personne et l’anonymat du narrateur, par ailleurs expressif, se conjuguent au caractère « phénoménologique » de la musique, au sens d’une mimesis de l’espace intérieur, afin d’attirer la sympathie du spectateur. Plusieurs éléments musicaux contribuent à cette impression : figures rhétoriques (tropes de distance, figures de marche, Seufzerfigur, etc.), usage significatif des modes majeur et mineur, subversion sémantique différents genres (valse, Volkslied, opéra, etc.), qualité subjective des ambivalences métriques et formelles, aspect médiatisé des sons qu’entend ou que s’imagine le voyageur, etc. L’effet d’aliénation (Verfremdungseffekt) provoqué par Die sieben Todsünden oeuvre dans un tout autre sens : il amène l’auditeur à adopter une attitude critique face à l’aliénation de la protagoniste « Anna ». Le ton narratif, la perversion des lieux communs (textuels et musicaux), l’aridité de la mélodie, l’ironie stylistique (usage sarcastique du style barbershop, du Choral protestant, du shimmy, du moto perpetuo, de la valse, etc.) et la tonalité élargie participent au ton narquois de l’oeuvre, incitant délibérément à une prise de distance critique.Alienation, the principal source of the modern malaise, denotes the state of a human being who is caught between what he is and what he ought to be. My dissertation will demonstrate that the depiction of this ontological deficiency in vocal music exists under different modalities, subjective and objective. Beguiled by a work dealing with the topic of alienation within the subjective mode, the listener is made vulnerable to its charm and sympathizes with its alienated protagonist. Colliding with a work of the objective type, the spectator discovers that he is confronted by a piece that seeks to prevent any emotional identification with the characters. Starting from, but not limited to, the perspective of traditional hermeneutics and criticism, my research aims at a deeper understanding of alienation in music during the modern Germanic period (within the limits of the 19th and 20th centuries). Franz Schubert’s (and Wilhelm Müller’s) Winterreise and Kurt Weill’s (and Bertolt Brecht’s) ballet-chanté Die sieben Todsünden exemplify the different modalities of alienation, subjective and objective respectively. I approach the concept of alienation from various angles : the first chapter retraces its development within a history of ideas (philosophy, theology, aesthetics, social sciences, psychoanalysis); chapters 2, 3, and 5 begin to study its subjective and objective articulations by investigating the genesis and reception of Winterreise and Die sieben Todsünden; analytical chapters 4 and 6 offer and an in-depth investigation into these works in relation to their particular modality of alienation. In Winterreise, many elements combine to confer a phenomenological quality to the music (understood as the mimesis of an interior, subjective space) in the hopes that it will stir the audience’s sympathy : note the presence of a double (the hurdy-gurdy player), first-person narration by an anonymous, yet expressive, speaker, and so on. Many musical features support the effect : different topoi (tropes of distance, marching and sighing figures, etc.), the symbolic use of major and minor modes, the subversion of meanings attributed to different genres (waltz, Volkslied, opera, etc.), the subjective quality of metrical and formal dissonances, and the mediated aspect of sounds that the wanderer hears or imagines. The alienation-effect (Verfremdungseffekt) caused by Die sieben Todsünden is altogether contrastive. It encourages its listener to take a critical attitude toward the alienation of Anna, the protagonist. The narrative tone, the distortion of commonplaces (literary and musical), the arid melodies, the ironic style (sarcastic use of barbershop music, Protestant chorals, the shimmy, moto perpetuo, the waltz, etc.), and tonal ambiguity contribute to the sardonic tone of a work that urges critical distance.Als weitgehend anerkannte Quelle des modernen Unbehagens beschreibt die Entfremdung den Zustand menschlichen Daseins in der Schwebe zwischen dem, was er ist, und dem, was er sein sollte. Meine Dissertation zeigt auf, dass die gesangliche Darstellung eines solchen Zustands ontologischer Defizienz sowohl eine subjektive als auch eine objektive Modalität haben kann. Sobald der Zuschauer der ersten, nämlich der subjektiven, Modalität begegnet, wird er durch das Werk verzaubert und sympathisiert mit dem entfremdeten Protagonisten. Sieht er sich wiederum mit der objektiven Modalität konfrontiert, ist es das Werk selbst, welches jeglichen Effekt einer gefühlsmäßigen Identifizierung mit der Hauptfigur verhindert. Bezug nehmend auf die hermeneutischen und kritischen Traditionen strebe ich nach einer Vertiefung des Entfremdungsbegriffs in der Musik der germanischen Moderne (innerhalb Grenzen des 19. und des 20. Jahrhunderts) in ihren verschiedenen Formen. Franz Schuberts (und Wilhelm Müllers„Winterreise“ sowie das gesungene Ballet „Die sieben Todsünden“ von Kurt Weill (und Bertolt Brecht) veranschaulichen jeweils die subjektive und die objecktive Modalität der Entfremdung. Die vorliegende Dissertation beleuchtet das Konzept der Entfremdung von verschiedenen Seiten: Das erste Kapitel vergegenwärtigt die Entwicklung der Ideengeschichte (Philosophie, Theologie, Ästhetik, Gesellschaftswissenschaften, Psychoanalyse); die Kapitel 2, 3 und 5 befassen sich mit dem Ausdruck ihrer verschiedenen Modalitäten in der Entstehung sowie der Rezeption der Winterreise und der Sieben Todsünden; die Kapitel 4 und 6 bieten vertiefende Analysen jedes einzelnen Werkes im Zusammenhang mit diesen Modalitäten. In der „Winterreise“ vereinigen sich die Präsenz des Doppelgängers (der Leiermann), die Ich Erzählung und die Anonymität des ansonsten sehr ausdrucksvollen Erzählers mit dem „phänomenologischen“ Charakter der Musik, im Sinne einer Mimesis des inneren Raums, um die Sympathie des Zuschauers anzusprechen. Mehrere musikalische Elemente tragen zu diesem Eindruck bei: Rhetorische Figuren (z.B. Distanz- und Wandermotive, Seufzerfiguren usw.), der signifikante Gebrauch von Dur und Moll, die semantische Subversion der verschiedenen Genres (Walzer, Volkslied, Oper, usw.), die subjektive Beschaffenheit metrischer und formaler Ambivalenzen, der mediatisierte Aspekt der Töne, die der Reisende hört oder sich vorstellt, usw. Der Verfremdungseffekt, der durch „Die sieben Todsünden“ hervorgerufen wird, ist ein gänzlich anderer: Er drängt den Zuhörer dazu, eine kritische Stellung in Hinblick auf die Entfremdung der Protagonistin „Anna“ zu beziehen. Der narrative Ton, die Pervertierung der textuellen und musikalischen Gemeinplätze, die stilistische Ironie (der sarkastische Gebrauch des barbershop-Stils, des protestantischen Chors, des shimmy, des moto perpetuo, des Walzers, usw.) und die allgemeine tonale sowie stilistische Zweideutigkeit tragen zum spöttischen Ton des Werks bei und führen so zur gewünschten kritischen Distanz

The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry

Netrins are guidance cues involvedinneural connectivity.Wehave shownthat the netrin-1 receptor DCC (deletedin colorectal cancer) is involvedinthefunctionalorganizationofthemesocorticolimbic dopamine(DA)system.Adult micewithaheterozygousloss-of-function mutation in dcc exhibit changes in indexes of DA function, including DA-related behaviors. These phenotypes are only observed after puberty,acritical periodinthe maturationofthe mesocortical DAprojection. Here, weexamined whether dcc heterozygous mice exhibit structural changes in medial prefrontal cortex (mPFC) DA synaptic connectivity, before and after puberty. Stereological counts of tyrosine-hydroxylase (TH)-positive varicosities were increased in the cingulate 1 and prelimbic regions of the pregenual mPFC. dcc heterozygous mice also exhibited alterations in the size, complexity, and dendritic spine density of mPFC layer V pyramidal neuron basilar dendritic arbors. Remarkably, these presynaptic and postsynaptic partner phenotypes were not observed in juvenile mice, suggesting that DCC selectively influences the extensive branching and synaptic differentiation that occurs in the maturing mPFC DA circuitatpuberty.Immunolabelingexperimentsinwild-typemice demonstratedthat DCCissegregatedtoTH-positivefibersinnervating the nucleus accumbens, with only scarce DCC labeling in mPFC TH-positive fibers. Netrin had an inverted target expression pattern. Thus, DCC-mediated netrin-1 signaling may influence the formation/maintenance of mesocorticolimbic DA topography. In support of this, we report that dcc heterozygous mice exhibit a twofold increase in the density of mPFC DCC/TH-positive varicosities. Our results implicate DCC-mediated netrin-1 signaling in the establishment of mPFC DA circuitry during puberty

Role of Netrin-1 Signaling in Nerve Regeneration.

Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A-D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery

The curious case of NG2 cells: transient trend or game changer?

It has been 10 years since the seminal work of Dwight Bergles and collaborators demonstrated that NG2 (nerve/glial antigen 2)-expressing oligodendrocyte progenitor cells (NG2 cells) receive functional glutamatergic synapses from neurons (Bergles et al., 2000), contradicting the old dogma that only neurons possess the complex and specialized molecular machinery necessary to receive synapses. While this surprising discovery may have been initially shunned as a novelty item of undefined functional significance, the study of neuron-to-NG2 cell neurotransmission has since become a very active and exciting field of research. Many laboratories have now confirmed and extended the initial discovery, showing for example that NG2 cells can also receive inhibitory GABAergic synapses (Lin and Bergles, 2004) or that neuron-to-NG2 cell synaptic transmission is a rather ubiquitous phenomenon that has been observed in all brain areas explored so far, including white matter tracts (Kukley et al., 2007; Ziskin et al., 2007; Etxeberria et al., 2010). Thus, while still being in its infancy, this field of research has already brought many surprising and interesting discoveries, and has become part of a continuously growing effort in neuroscience to re-evaluate the long underestimated role of glial cells in brain function (Barres, 2008). However, this area of research is now reaching an important milestone and its long-term significance will be defined by its ability to uncover the still elusive function of NG2 cells and their synapses in the brain, rather than by its sensational but transient successes at upsetting the old order established by neuronal physiology. To participate in the effort to facilitate such a transition, here we propose a critical review of the latest findings in the field of NG2 cell physiology – discussing how they inform us on the possible function(s) of NG2 cells in the brain – and we present some personal views on new directions the field could benefit from in order to achieve lasting significance

Peri-Pubertal Emergence of UNC-5 Homologue Expression by Dopamine Neurons in Rodents

Puberty is a critical period in mesocorticolimbic dopamine (DA) system development, particularly for the medial prefrontal cortex (mPFC) projection which achieves maturity in early adulthood. The guidance cue netrin-1 organizes neuronal networks by attracting or repelling cellular processes through DCC (deleted in colorectal cancer) and UNC-5 homologue (UNC5H) receptors, respectively. We have shown that variations in netrin-1 receptor levels lead to selective reorganization of mPFC DA circuitry, and changes in DA-related behaviors, in transgenic mice and in rats. Significantly, these effects are only observed after puberty, suggesting that netrin-1 mediated effects on DA systems vary across development. Here we report on the normal expression of DCC and UNC5H in the ventral tegmental area (VTA) by DA neurons from embryonic life to adulthood, in both mice and rats. We show a dramatic and enduring pubertal change in the ratio of DCC:UNC5H receptors, reflecting a shift toward predominant UNC5H function. This shift in DCC:UNC5H ratio coincides with the pubertal emergence of UNC5H expression by VTA DA neurons. Although the distribution of DCC and UNC5H by VTA DA neurons changes during puberty, the pattern of netrin-1 immunoreactivity in these cells does not. Together, our findings suggest that DCC:UNC5H ratios in DA neurons at critical periods may have important consequences for the organization and function of mesocorticolimbic DA systems

Netrin Inhibits Regenerative Axon Growth of Adult Dorsal Root Ganglion Neurons in Vitro

Netrin is a neuronal guidance molecule implicated in the development of spinal commissural neurons and cortical neurons. The attractive function of netrin requires the receptor, Deleted in Colorectal Cancer (DCC), while the receptor Unc5h is involved in the repulsive action of netrin during embryonic development. Although the expression of netrin and its receptor has been demonstrated in the adult nervous system, the function of netrin in adult neurons has not yet been elucidated. Here, we show that netrin treatment inhibited neurite outgrowth of adult dorsal root ganglion (DRG) neurons in explant and dissociated cultures. In addition, unc5h1-3 mRNAs, but not the dcc mRNA, are abundantly expressed in the adult DRG. An in situ hybridization study demonstrated that unc5h mRNAs were expressed in DRG neurons. This finding indicates that netrin/Unc5h signaling may play a role in the neurite outgrowth of adult DRG neurons and that netrin may be involved in the regulation of peripheral nerve regeneration

DCC confers susceptibility to depression-like behaviors in humans and mice and is regulated by miR-218

Variations in the expression of the Netrin-1 guidance cue receptor DCC (deleted in colorectal cancer) appear to confer resilience or susceptibility to psychopathologies involving prefrontal cortex (PFC) dysfunction.With the use of postmortem brain tissue, mouse models of defeat stress, and in vitro analysis, we assessed microRNA (miRNA) regulation of DCC and whether changes in DCC levels in the PFC lead to vulnerability to depression-like behaviors.We identified miR-218 as a posttranscriptional repressor of DCC and detected coexpression of DCC and miR-218 in pyramidal neurons of human and mouse PFC. We found that exaggerated expression of DCC and reduced levels of miR-218 in the PFC are consistent traits of mice susceptible to chronic stress and of major depressive disorder in humans. Remarkably, upregulation of Dcc in mouse PFC pyramidal neurons causes vulnerability to stress-induced social avoidance and anhedonia.These data are the first demonstration of microRNA regulation of DCC and suggest that, by regulating DCC, miR-218 may be a switch of susceptibility versus resilience to stress-related disorders

Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Recent studies suggest a variety of factors characterize substantia nigra neurons vulnerable to Parkinson's disease, including the transcription factors pituitary homeobox 3 (Pitx3) and orthodenticle homeobox 2 (Otx2) and the trophic factor receptor deleted in colorectal cancer (DCC), but there is limited information on their expression and localization in adult humans. Pitx3, Otx2, and DCC were immunohistochemically localized in the upper brainstem of adult humans and mice and protein expression assessed using relative intensity measures and online microarray data. Pitx3 was present and highly expressed in most dopamine neurons. Surprisingly, in our elderly subjects no Otx2 immunoreactivity was detected in dopamine neurons, although Otx2 gene expression was found in younger cases. Enhanced DCC gene expression occurred in the substantia nigra, and higher amounts of DCC protein characterized vulnerable ventral nigral dopamine neurons. Our data show that, at the age when Parkinson's disease typically occurs, there are no significant differences in the expression of transcription factors in brainstem dopamine neurons, but those most vulnerable to Parkinson's disease rely more on the trophic factor receptor DCC than other brainstem dopamine neurons

Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons.

Extrinsic cues trigger the local translation of specific mRNAs in growing axons via cell surface receptors. The coupling of ribosomes to receptors has been proposed as a mechanism linking signals to local translation but it is not known how broadly this mechanism operates, nor whether it can selectively regulate mRNA translation. We report that receptor-ribosome coupling is employed by multiple guidance cue receptors and this interaction is mRNA-dependent. We find that different receptors associate with distinct sets of mRNAs and RNA-binding proteins. Cue stimulation of growing Xenopus retinal ganglion cell axons induces rapid dissociation of ribosomes from receptors and the selective translation of receptor-specific mRNAs. Further, we show that receptor-ribosome dissociation and cue-induced selective translation are inhibited by co-exposure to translation-repressive cues, suggesting a novel mode of signal integration. Our findings reveal receptor-specific interactomes and suggest a generalizable model for cue-selective control of the local proteome

Canonical BMP–Smad Signalling Promotes Neurite Growth in Rat Midbrain Dopaminergic Neurons

Ventral midbrain (VM) dopaminergic (DA) neurons project to the dorsal striatum via the nigrostriatal pathway to regulate voluntary movements, and their loss leads to the motor dysfunction seen in Parkinson’s disease (PD). Despite recent progress in the understanding of VM DA neurogenesis, the factors regulating nigrostriatal pathway development remain largely unknown. The bone morphogenetic protein (BMP) family regulates neurite growth in the developing nervous system and may contribute to nigrostriatal pathway development. Two related members of this family, BMP2 and growth differentiation factor (GDF)5, have neurotrophic effects, including promotion of neurite growth, on cultured VM DA neurons. However, the molecular mechanisms regulating their effects on DA neurons are unknown. By characterising the temporal expression profiles of endogenous BMP receptors (BMPRs) in the developing and adult rat VM and striatum, this study identified BMP2 and GDF5 as potential regulators of nigrostriatal pathway development. Furthermore, through the use of noggin, dorsomorphin and BMPR/Smad plasmids, this study demonstrated that GDF5- and BMP2-induced neurite outgrowth from cultured VM DA neurons is dependent on BMP type I receptor activation of the Smad 1/5/8 signalling pathway