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Learning, attention and action play a crucial role in determining how stimulus predictions are formed, stored, and updated. Years-long experience with the specific repertoires of sounds of one or more musical styles is what characterizes professional musicians. Here we contrasted active experience with sounds, namely long-lasting motor practice, theoretical study and engaged listening to the acoustic features characterizing a musical style of choice in professional musicians with mainly passive experience of sounds in laypersons. We hypothesized that long-term active experience of sounds would influence the neural predictions of the stylistic features in professional musicians in a distinct way from the mainly passive experience of sounds in laypersons. Participants with different musical backgrounds were recruited: professional jazz and classical musicians, amateur musicians and non-musicians. They were presented with a musical multi-feature paradigm eliciting mismatch negativity (MMN), a prediction error signal to changes in six sound features for only 12 minutes of electroencephalography (EEG) and magnetoencephalography (MEG) recordings. We observed a generally larger MMN amplitudes-indicative of stronger automatic neural signals to violated priors-in jazz musicians (but not in classical musicians) as compared to non-musicians and amateurs. The specific MMN enhancements were found for spectral features (timbre, pitch, slide) and sound intensity. In participants who were not musicians, the higher preference for jazz music was associated with reduced MMN to pitch slide (a feature common in jazz music style). Our results suggest that long-lasting, active experience of a musical style is associated with accurate neural priors for the sound features of the preferred style, in contrast to passive listening.
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Estimulación Acústica/métodos , Percepción Sonora/fisiología , Percepción de la Altura Tonal/fisiología , Adulto , Electroencefalografía , Femenino , Humanos , Magnetoencefalografía , Masculino , Música , Adulto JovenRESUMEN
Music is often used to regulate emotions and mood. Typically, music conveys and induces emotions even when one does not attend to them. Studies on the neural substrates of musical emotions have, however, only examined brain activity when subjects have focused on the emotional content of the music. Here we address with functional magnetic resonance imaging (fMRI) the neural processing of happy, sad, and fearful music with a paradigm in which 56 subjects were instructed to either classify the emotions (explicit condition) or pay attention to the number of instruments playing (implicit condition) in 4-s music clips. In the implicit vs. explicit condition, stimuli activated bilaterally the inferior parietal lobule, premotor cortex, caudate, and ventromedial frontal areas. The cortical dorsomedial prefrontal and occipital areas activated during explicit processing were those previously shown to be associated with the cognitive processing of music and emotion recognition and regulation. Moreover, happiness in music was associated with activity in the bilateral auditory cortex, left parahippocampal gyrus, and supplementary motor area, whereas the negative emotions of sadness and fear corresponded with activation of the left anterior cingulate and middle frontal gyrus and down-regulation of the orbitofrontal cortex. Our study demonstrates for the first time in healthy subjects the neural underpinnings of the implicit processing of brief musical emotions, particularly in frontoparietal, dorsolateral prefrontal, and striatal areas of the brain.
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Atención/fisiología , Mapeo Encefálico , Encéfalo/fisiología , Emociones/fisiología , Música , Estimulación Acústica , Adulto , Encéfalo/diagnóstico por imagen , Miedo , Femenino , Felicidad , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Estimulación Luminosa , Adulto JovenRESUMEN
Low-level (timbral) and high-level (tonal and rhythmical) musical features during continuous listening to music, studied by functional magnetic resonance imaging (fMRI), have been shown to elicit large-scale responses in cognitive, motor, and limbic brain networks. Using a similar methodological approach and a similar group of participants, we aimed to study the replicability of previous findings. Participants' fMRI responses during continuous listening of a tango Nuevo piece were correlated voxelwise against the time series of a set of perceptually validated musical features computationally extracted from the music. The replicability of previous results and the present study was assessed by two approaches: (a) correlating the respective activation maps, and (b) computing the overlap of active voxels between datasets at variable levels of ranked significance. Activity elicited by timbral features was better replicable than activity elicited by tonal and rhythmical ones. These results indicate more reliable processing mechanisms for low-level musical features as compared to more high-level features. The processing of such high-level features is probably more sensitive to the state and traits of the listeners, as well as of their background in music.
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Percepción Auditiva/fisiología , Encéfalo/fisiología , Música , Estimulación Acústica , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Music therapists use guided affect regulation in the treatment of mood disorders. However, self-directed uses of music in affect regulation are not fully understood. Some uses of music may have negative effects on mental health, as can non-music regulation strategies, such as rumination. Psychological testing and functional magnetic resonance imaging (fMRI) were used explore music listening strategies in relation to mental health. Participants (n = 123) were assessed for depression, anxiety and Neuroticism, and uses of Music in Mood Regulation (MMR). Neural responses to music were measured in the medial prefrontal cortex (mPFC) in a subset of participants (n = 56). Discharge, using music to express negative emotions, related to increased anxiety and Neuroticism in all participants and particularly in males. Males high in Discharge showed decreased activity of mPFC during music listening compared with those using less Discharge. Females high in Diversion, using music to distract from negative emotions, showed more mPFC activity than females using less Diversion. These results suggest that the use of Discharge strategy can be associated with maladaptive patterns of emotional regulation, and may even have long-term negative effects on mental health. This finding has real-world applications in psychotherapy and particularly in clinical music therapy.
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Emotion-related areas of the brain, such as the medial frontal cortices, amygdala, and striatum, are activated during listening to sad or happy music as well as during listening to pleasurable music. Indeed, in music, like in other arts, sad and happy emotions might co-exist and be distinct from emotions of pleasure or enjoyment. Here we aimed at discerning the neural correlates of sadness or happiness in music as opposed those related to musical enjoyment. We further investigated whether musical expertise modulates the neural activity during affective listening of music. To these aims, 13 musicians and 16 non-musicians brought to the lab their most liked and disliked musical pieces with a happy and sad connotation. Based on a listening test, we selected the most representative 18 sec excerpts of the emotions of interest for each individual participant. Functional magnetic resonance imaging (fMRI) recordings were obtained while subjects listened to and rated the excerpts. The cortico-thalamo-striatal reward circuit and motor areas were more active during liked than disliked music, whereas only the auditory cortex and the right amygdala were more active for disliked over liked music. These results discern the brain structures responsible for the perception of sad and happy emotions in music from those related to musical enjoyment. We also obtained novel evidence for functional differences in the limbic system associated with musical expertise, by showing enhanced liking-related activity in fronto-insular and cingulate areas in musicians.
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Mounting evidence links the enjoyment of music to brain areas implicated in emotion and the dopaminergic reward system. In particular, dopamine release in the ventral striatum seems to play a major role in the rewarding aspect of music listening. Striatal dopamine also influences reinforcement learning, such that subjects with greater dopamine efficacy learn better to approach rewards while those with lesser dopamine efficacy learn better to avoid punishments. In this study, we explored the practical implications of musical pleasure through its ability to facilitate reinforcement learning via non-pharmacological dopamine elicitation. Subjects from a wide variety of musical backgrounds chose a pleasurable and a neutral piece of music from an experimenter-compiled database, and then listened to one or both of these pieces (according to pseudo-random group assignment) as they performed a reinforcement learning task dependent on dopamine transmission. We assessed musical backgrounds as well as typical listening patterns with the new Helsinki Inventory of Music and Affective Behaviors (HIMAB), and separately investigated behavior for the training and test phases of the learning task. Subjects with more musical experience trained better with neutral music and tested better with pleasurable music, while those with less musical experience exhibited the opposite effect. HIMAB results regarding listening behaviors and subjective music ratings indicate that these effects arose from different listening styles: namely, more affective listening in non-musicians and more analytical listening in musicians. In conclusion, musical pleasure was able to influence task performance, and the shape of this effect depended on group and individual factors. These findings have implications in affective neuroscience, neuroaesthetics, learning, and music therapy.
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Music is often studied as a cognitive domain alongside language. The emotional aspects of music have also been shown to be important, but views on their nature diverge. For instance, the specific emotions that music induces and how they relate to emotional expression are still under debate. Here we propose a mental and neural chronometry of the aesthetic experience of music initiated and mediated by external and internal contexts such as intentionality, background mood, attention, and expertise. The initial stages necessary for an aesthetic experience of music are feature analysis, integration across modalities, and cognitive processing on the basis of long-term knowledge. These stages are common to individuals belonging to the same musical culture. The initial emotional reactions to music include the startle reflex, core "liking," and arousal. Subsequently, discrete emotions are perceived and induced. Presumably somatomotor processes synchronizing the body with the music also come into play here. The subsequent stages, in which cognitive, affective, and decisional processes intermingle, require controlled cross-modal neural processes to result in aesthetic emotions, aesthetic judgments, and conscious liking. These latter aesthetic stages often require attention, intentionality, and expertise for their full actualization.
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Musical emotions, such as happiness and sadness, have been investigated using instrumental music devoid of linguistic content. However, pop and rock, the most common musical genres, utilize lyrics for conveying emotions. Using participants' self-selected musical excerpts, we studied their behavior and brain responses to elucidate how lyrics interact with musical emotion processing, as reflected by emotion recognition and activation of limbic areas involved in affective experience. We extracted samples from subjects' selections of sad and happy pieces and sorted them according to the presence of lyrics. Acoustic feature analysis showed that music with lyrics differed from music without lyrics in spectral centroid, a feature related to perceptual brightness, whereas sad music with lyrics did not diverge from happy music without lyrics, indicating the role of other factors in emotion classification. Behavioral ratings revealed that happy music without lyrics induced stronger positive emotions than happy music with lyrics. We also acquired functional magnetic resonance imaging data while subjects performed affective tasks regarding the music. First, using ecological and acoustically variable stimuli, we broadened previous findings about the brain processing of musical emotions and of songs versus instrumental music. Additionally, contrasts between sad music with versus without lyrics recruited the parahippocampal gyrus, the amygdala, the claustrum, the putamen, the precentral gyrus, the medial and inferior frontal gyri (including Broca's area), and the auditory cortex, while the reverse contrast produced no activations. Happy music without lyrics activated structures of the limbic system and the right pars opercularis of the inferior frontal gyrus, whereas auditory regions alone responded to happy music with lyrics. These findings point to the role of acoustic cues for the experience of happiness in music and to the importance of lyrics for sad musical emotions.
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Biologically active peptides are synthesized from inactive pre-proproteins or peptide precursors by the sequential actions of processing enzymes. Proprotein convertases cleave the precursor at pairs of basic amino acids, which are then removed from the carboxyl terminus of the generated fragments by a specific carboxypeptidase. Caenorhabditis elegans strains lacking proprotein convertase EGL-3 display a severely impaired neuropeptide profile (Husson et al. 2006, J. Neurochem.98, 1999-2012). In the present study, we examined the role of the C. elegans carboxypeptidase E orthologue EGL-21 in the processing of peptide precursors. More than 100 carboxy-terminally extended neuropeptides were detected in egl-21 mutant strains. These findings suggest that EGL-21 is a major carboxypeptidase involved in the processing of FMRFamide-like peptide (FLP) precursors and neuropeptide-like protein (NLP) precursors. The impaired peptide profile of egl-3 and egl-21 mutants is reflected in some similar phenotypes. They both share a severe widening of the intestinal lumen, locomotion defects, and retention of embryos. In addition, egl-3 animals have decreased intestinal fat content. Taken together, these results suggest that EGL-3 and EGL-21 are key enzymes for the proper processing of neuropeptides that control egg-laying, locomotion, fat storage and the nutritional status.
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Proteínas de Caenorhabditis elegans/fisiología , Caenorhabditis elegans/enzimología , Carboxipeptidasa H/fisiología , Neuropéptidos/fisiología , Alelos , Animales , Caenorhabditis elegans/genética , Carboxipeptidasa H/genética , Cromatografía Líquida de Alta Presión , Espectrometría de Masas , Oxazinas , Péptidos/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
BACKGROUND: Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 (FMR1) gene. How FMR1 affects the function of the central and peripheral nervous systems is still unclear. FMR1 is an RNA binding protein that associates with a small percentage of total mRNAs in vivo. It remains largely unknown what proteins encoded by mRNAs in the FMR1-messenger ribonuclear protein (mRNP) complex are most relevant to the affected physiological processes. RESULTS: Loss-of-function mutations in the Drosophila fragile X-related (dfmr1) gene, which is highly homologous to the human fmr1 gene, decrease the duration and percentage of time that crawling larvae spend on linear locomotion. Overexpression of DFMR1 in multiple dendritic (MD) sensory neurons increases the time percentage and duration of linear locomotion; this phenotype is similar to that caused by reduced expression of the MD neuron subtype-specific degenerin/epithelial sodium channel (DEG/ENaC) family protein Pickpocket1 (PPK1). Genetic analyses indicate that PPK1 is a key component downstream of DFMR1 in controlling the crawling behavior of Drosophila larvae. DFMR1 and ppk1 mRNA are present in the same mRNP complex in vivo and can directly bind to each other in vitro. DFMR1 downregulates the level of ppk1 mRNA in vivo, and this regulatory process also involves Argonaute2 (Ago2), a key component in the RNA interference pathway. CONCLUSIONS: These studies identify ppk1 mRNA as a physiologically relevant in vivo target of DFMR1. Our finding that the level of ppk1 mRNA is regulated by DFMR1 and Ago2 reveals a genetic pathway that controls sensory input-modulated locomotion behavior.
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Regulación de la Expresión Génica , Locomoción/fisiología , Proteínas del Tejido Nervioso/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN , Ribonucleoproteínas/metabolismo , Canales de Sodio/metabolismo , Animales , Animales Modificados Genéticamente , Proteínas Argonautas , Cruzamientos Genéticos , Cartilla de ADN , ADN Complementario/genética , Drosophila , Proteínas de Drosophila/metabolismo , Electroforesis en Gel de Agar , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Larva/fisiología , Locomoción/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/fisiología , Neuronas Aferentes/metabolismo , Pruebas de Precipitina , Interferencia de ARN/fisiología , Complejo Silenciador Inducido por ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Canales de Sodio/genéticaRESUMEN
Protein translocons of the mammalian endoplasmic reticulum are composed of numerous functional components whose organization during different stages of the transport cycle in vivo remains poorly understood. We have developed generally applicable methods based on fluorescence resonance energy transfer (FRET) to probe the relative proximities of endogenously expressed translocon components in cells. Examination of substrate-engaged translocons revealed oligomeric assemblies of the Sec61 complex that were associated to varying degrees with other essential components including the signal recognition particle receptor TRAM and the TRAP complex. Remarkably, these components not only remained assembled but also had a similar, yet distinguishable, organization both during and after nascent chain translocation. The persistence of preassembled and complete translocons between successive rounds of transport may facilitate highly efficient translocation in vivo despite temporal constraints imposed by ongoing translation and a crowded cellular environment.
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Retículo Endoplásmico/metabolismo , Transporte de Proteínas/fisiología , Animales , Línea Celular , Perros , Riñón , Glicoproteínas de Membrana/metabolismoRESUMEN
Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 gene. How these mutations affect neuronal development and function remains largely elusive. We generated specific point mutations or small deletions in the Drosophila fragile X-related (Fmr1) gene and examined the roles of Fmr1 in dendritic development of dendritic arborization (DA) neurons in Drosophila larvae. We found that Fmr1 could be detected in the cell bodies and proximal dendrites of DA neurons and that Fmr1 loss-of-function mutations increased the number of higher-order dendritic branches. Conversely, overexpression of Fmr1 in DA neurons dramatically decreased dendritic branching. In dissecting the mechanisms underlying Fmr1 function in dendrite development, we found that the mRNA encoding small GTPase Rac1 was present in the Fmr1-messenger ribonucleoprotein complexes in vivo. Mosaic analysis with a repressor cell marker (MARCM) and overexpression studies revealed that Rac1 has a cell-autonomous function in promoting dendritic branching of DA neurons. Furthermore, Fmr1 and Rac1 genetically interact with each other in controlling the formation of fine dendritic branches. These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect.
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Dendritas/metabolismo , Proteínas de Drosophila , Drosophila/crecimiento & desarrollo , Sistema Nervioso/crecimiento & desarrollo , Proteínas de Unión al ARN/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Animales , Drosophila/enzimología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Larva/crecimiento & desarrollo , Mutación , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Ribonucleoproteínas/metabolismo , Proteína de Unión al GTP rac1/genéticaRESUMEN
How the dendritic branching patterns of different neurons are specified is a fascinating question in developmental neurobiology. This question can now be addressed in detail in Drosophila, owing to technological advances that allow in vivo labeling of the dendrites of identifiable neurons. Recent genetic analyses in flies have uncovered several molecules, including transcription factors, cytoskeleton-associated proteins and membrane receptor-like molecules, that provide a glimpse into the complex regulatory network that controls dendritic morphogenesis.
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Dendritas/genética , Regulación del Desarrollo de la Expresión Génica , Morfogénesis/fisiología , Animales , Drosophila/genética , Drosophila/fisiología , Genes de Insecto , Neuronas/fisiologíaRESUMEN
Although the transport of model proteins across the mammalian ER can be reconstituted with purified Sec61p complex, TRAM, and signal recognition particle receptor, some substrates, such as the prion protein (PrP), are inefficiently or improperly translocated using only these components. Here, we purify a factor needed for proper translocation of PrP and identify it as the translocon-associated protein (TRAP) complex. Surprisingly, TRAP also stimulates vectorial transport of many, but not all, other substrates in a manner influenced by their signal sequences. Comparative analyses of several natural signal sequences suggest that a dependence on TRAP for translocation is not due to any single physical parameter, such as hydrophobicity of the signal sequence. Instead, a functional property of the signal, efficiency of its post-targeting role in initiating substrate translocation, correlates inversely with TRAP dependence. Thus, maximal translocation independent of TRAP can only be achieved with a signal sequence, such as the one from prolactin, whose strong interaction with the translocon mediates translocon gating shortly after targeting. These results identify the TRAP complex as a functional component of the translocon and demonstrate that it acts in a substrate-specific manner to facilitate the initiation of protein translocation.