Differences in Human Cortical Gene Expression Match the Temporal Properties of Large-Scale Functional Networks

International audienceWe explore the relationships between the cortex functional organization and genetic expression (as provided by the Allen Human Brain Atlas). Previous work suggests that functional cortical networks (resting state and task based) are organized as two large networks (differentiated by their preferred information processing mode) shaped like two rings. The first ring–Visual-Sensorimotor-Auditory (VSA)–comprises visual, auditory, somatosensory, and motor cortices that process real time world interactions. The second ring–Parieto-Temporo-Frontal (PTF)–comprises parietal, temporal, and frontal regions with networks dedicated to cognitive functions, emotions, biological needs, and internally driven rhythms. We found–with correspondence analysis–that the patterns of expression of the 938 genes most differentially expressed across the cortex organized the cortex into two sets of regions that match the two rings. We confirmed this result using discriminant correspondence analysis by showing that the genetic profiles of cortical regions can reliably predict to what ring these regions belong. We found that several of the proteins–coded by genes that most differentiate the rings–were involved in neuronal information processing such as ionic channels and neurotransmitter release. The systematic study of families of genes revealed specific proteins within families preferentially expressed in each ring. The results showed strong congruence between the preferential expression of subsets of genes, temporal properties of the proteins they code, and the preferred processing modes of the rings. Ionic channels and release-related proteins more expressed in the VSA ring favor temporal precision of fast evoked neural transmission (Sodium channels SCNA1, SCNB1 potassium channel KCNA1, calcium channel CACNA2D2, Synaptotagmin SYT2, Complexin CPLX1, Synaptobrevin VAMP1). Conversely, genes expressed in the PTF ring favor slower, sustained, or rhythmic activation (Sodium channels SCNA3, SCNB3, SCN9A potassium channels KCNF1, KCNG1) and facilitate spontaneous transmitter release (calcium channel CACNA1H, Synaptotagmins SYT5, Complexin CPLX3, and synaptobrevin VAMP2)

Prof. Dr. Jorge Bossi (1934-2020): padre de la geología moderna de Uruguay

A synthesis of the academic and scientific activity developed by Prof. Dr. Jorge Bossi, for more than 60 years dedicated to the study of Uruguayan geology, is presented. This article is a review of his university teaching work and a tribute to his fruitful academic and scientific work on the geology of Uruguay and the region. His contributions have decisively influenced the current understanding of the tectonic evolution, stratigraphy and mineral resources of an important part of South America and southern Africa.Se presenta una síntesis de la actividad académica y científica desarrollada por el Prof. Dr. Jorge Bossi durante más de 60 años dedicados al estudio de la geología de Uruguay. El presente trabajo es una reseña de su labor docente y un homenaje a su fecunda labor académica y científica sobre la geología de Uruguay y la región. Sus aportes han influido de forma decisiva en la actual comprensión de la evolución tectónica, la estratigrafía y los recursos minerales de una parte importante de Sudamérica y África meridional

Madera enigmática y primera evidencia de tetrápodos en Formación Yaguarí (Pérmico medio-superior), Uruguay

This article describes an intriguing fossil material recently found in the fine-grained sandstone levels from the upper section of the Yaguarí Formation of Uruguay. The nature of this specimen and its relationships were, initially, not easy to determine with confidence although it was subjected to several analyses, such as morphological and comparative examination complemented with preparation of thin sections and microanatomical and chemical studies under SEM. However, the anatomical structure shown in the performed transversal thin sections allowed solving the issue on the different animal or plant interpretations of the fossil specimen, which was finally discerned in favor of the latter. Therefore, after a detailed comparative study of the thin sections, we concluded that the specimen is a wood fragment related to the Dadoxylon-Araucarioxylon complex. Moreover, in order to provide a better biostratigraphic calibration for these deposits until now devoid of fossils, we include a preliminary description of recently found fossil footprints, which represent the first evidence of the presence of tetrapods in levels of the Yaguarí Formation (sensu Elizalde et al., 1970), below the conglomerates that have yielded the Colonia Orozco Fauna. The footprints were preliminary assigned to the ichnotaxa cf. Karoopes isp, cf. Capitosauroides isp., and cf. Pachypes isp., suggesting the presence of gorgonopsids and therocephalian therapsids and pareiasauromorphs, respectively. The Middle-Late Permian age recently suggested for the Yaguarí Formation based on paleomagnetic and radioisotopic studies is here supported by the described fossils, which thus constitute preliminary but nonetheless relevant discoveries for deposits whose fossiliferous potential has yet to be explored.Este artículo describe un intrigante fósil recientemente descubierto en niveles de areniscas finas a medias de la sección superior de la Formación Yaguarí de Uruguay. La naturaleza y las afinidades de este espécimen no fueron inicialmente fáciles de determinar, a pesar de ser sometido a numerosos estudios, incluido un análisis anatómico-comparativo complementado con la preparación de secciones delgadas y análisis de su microestructura bajo Microscopio Electrónico de Barrido. La microestructura mostrada por las láminas delgadas en corte transversal permitió finalmente resolver el problema sobre discernir entre una naturaleza animal o vegetal del espécimen, siendo la última la aceptada. El detallado estudio comparativo de las secciones delgadas reveló que el espécimen es un fragmento de madera relacionado al complejo Dadoxylon-Araucarioxylon. Asimismo, para proveer una mejor calibración temporal de los depósitos de la sección superior de la Formación Yaguarí (Miembro Villa Viñoles), también se incluye en este trabajo una descripción preliminar de huellas de tetrápodos recientemente halladas en esta unidad, las cuales representan la primera evidencia de la presencia de tetrápodos en niveles de la Formación Yaguarí (sensu Elizalde et al., 1970) subyacentes a los conglomerados portadores de la Fauna de Colonia Orozco. Las huellas fueron asignadas a los icnotaxa cf. Karoopes isp., cf. Capitosauroides isp. y cf. Pachypes isp., sugiriendo la presencia de terápsidos gorgonópsidos y therocefalidos y de pareiasauromorfos, respectivamente. La edad Pérmico Medio a Tardío recientemente sugerida para la Formación Yaguarí, basado en estudios de paleomagnetismo sustentados por dataciones radioisotópicas, es congruente con la aportada por los fósiles aquí descriptos, que, aunque fragmentarios, constituyen descubrimientos preliminarmente relevantes para depósitos cuyo potencial fosilífero no ha sido aún explorado.CSIC: I+D 2016_24

Organisation multi-échelle du cortex humain : des réseaux anatomo-fonctioneles à l'expression des gènes

This work is conceived in the present panorama of fast development of large databases gathering experimental results about the organization of the human brain at different scales. This abundance of information calls for an intra and inter-disciplinary effort aimed to synthesize this information in a coherent way.The aim of this thesis was to contribute to this effort for knowledge synthesis to better understand the multiscale organization of the cerebral cortex. The work followed two paths: an intra-disciplinary effort to bring together results produced by the brain imaging community with particular focus on Resting State and Task Based MRI experiments; an inter-disciplinary attempt to draw a link between the anatomo-functional organization of the cortex as emerging from brain imaging studies and the cortical patterns of gene expression as revealed by recently published atlases of the adult human brain transcriptome.The thesis is organized into three parts: In Part I studied the anatomo-functional organization of the human cortex starting from brain imaging studies. In Part II we studied the link between cortical gene expression and the anatomo-functional organization of the cortex both in term of their topography and in term of their function, focusing in particular on information processing and memory formation. In Part III we present a platform that we developed to favor knowledge integration between cognitive networks and gene expression databases.In perspective we show how our approach may provide new insights to the debate about neurodegenerative and psychiatric diseases on one hand, modeling of dynamical processes in different areas of the cortex on the other.Ce travail est conçu dans le panorama de développement rapide de grandes bases de données qui rassemblent des ensembles de résultats expérimentaux sur l’organisation anatomo-fonctionnelle du cerveau humain à différentes échelles; l’abondance d’informations demande un effort intra et interdisciplinaire pour les synthétiser de façon cohérente. Le but de cette thèse est de contribuer à cet effort de synthèse. Le travail suit deux chemins: intra disciplinaire pour relier et synthétiser les résultats produits par la communauté de l’imagerie cérébrale, avec une focalisation particulière sur les Réseaux de Repos et les Réseaux Cognitifs; inter-disciplinaire pour relier l’organisation anatomo-fonctionnelle du cortex cérébral (résultats en imagerie cérébrale), et les expressions des gènes révélées par les bases de données publiées très récemment sur le transcriptome humain.Cette thèse est organisée en trois parties: dans Partie I nous étudions l’organisation anatomo-fonctionnelle du cortex à partir des études d’imagerie cérébrale. Dans la Partie II, nous étudions les liens entre l’expression corticale des gènes et l’organisation anatomo-fonctionnelle du cortex, à la fois en termes de similitude topographique et de congruence de fonction, en se focalisant en particulier sur le traitement de l’information et la mémorisation. Dans la Partie III, nous présentons une plate-forme pour intégrer dans une même représentation les données d’imagerie cérébrale et d’expression génétique.En perspective, nous montrons comment notre approche pourrait donner des nouveaux points de vu au débat sur les maladies neurodégénératives et psychiatriques, et sur les modelés des dynamiques corticales

Multiscale organization of the human cortex : from anatomo-functional cognitive networks to gene expression

Ce travail est conçu dans le panorama de développement rapide de grandes bases de données qui rassemblent des ensembles de résultats expérimentaux sur l’organisation anatomo-fonctionnelle du cerveau humain à différentes échelles; l’abondance d’informations demande un effort intra et interdisciplinaire pour les synthétiser de façon cohérente. Le but de cette thèse est de contribuer à cet effort de synthèse. Le travail suit deux chemins: intra disciplinaire pour relier et synthétiser les résultats produits par la communauté de l’imagerie cérébrale, avec une focalisation particulière sur les Réseaux de Repos et les Réseaux Cognitifs; inter-disciplinaire pour relier l’organisation anatomo-fonctionnelle du cortex cérébral (résultats en imagerie cérébrale), et les expressions des gènes révélées par les bases de données publiées très récemment sur le transcriptome humain.Cette thèse est organisée en trois parties: dans Partie I nous étudions l’organisation anatomo-fonctionnelle du cortex à partir des études d’imagerie cérébrale. Dans la Partie II, nous étudions les liens entre l’expression corticale des gènes et l’organisation anatomo-fonctionnelle du cortex, à la fois en termes de similitude topographique et de congruence de fonction, en se focalisant en particulier sur le traitement de l’information et la mémorisation. Dans la Partie III, nous présentons une plate-forme pour intégrer dans une même représentation les données d’imagerie cérébrale et d’expression génétique.En perspective, nous montrons comment notre approche pourrait donner des nouveaux points de vu au débat sur les maladies neurodégénératives et psychiatriques, et sur les modelés des dynamiques corticales.This work is conceived in the present panorama of fast development of large databases gathering experimental results about the organization of the human brain at different scales. This abundance of information calls for an intra and inter-disciplinary effort aimed to synthesize this information in a coherent way.The aim of this thesis was to contribute to this effort for knowledge synthesis to better understand the multiscale organization of the cerebral cortex. The work followed two paths: an intra-disciplinary effort to bring together results produced by the brain imaging community with particular focus on Resting State and Task Based MRI experiments; an inter-disciplinary attempt to draw a link between the anatomo-functional organization of the cortex as emerging from brain imaging studies and the cortical patterns of gene expression as revealed by recently published atlases of the adult human brain transcriptome.The thesis is organized into three parts: In Part I studied the anatomo-functional organization of the human cortex starting from brain imaging studies. In Part II we studied the link between cortical gene expression and the anatomo-functional organization of the cortex both in term of their topography and in term of their function, focusing in particular on information processing and memory formation. In Part III we present a platform that we developed to favor knowledge integration between cognitive networks and gene expression databases.In perspective we show how our approach may provide new insights to the debate about neurodegenerative and psychiatric diseases on one hand, modeling of dynamical processes in different areas of the cortex on the other

LinkRbrain: Multi-scale data integrator of the brain

International audienceBackgroundLinkRbrain is an open-access web platform for multi-scale data integration and visualization of human brain data. This platform integrates anatomical, functional, and genetic knowledge produced by the scientific community.New methodThe linkRbrain platform has two major components: (1) a data aggregation component that integrates multiple open databases into a single platform with a unified representation; and (2) a website that provides fast multi-scale integration and visualization of these data and makes the results immediately available.ResultsLinkRbrain allows users to visualize functional networks or/and genetic expression over a standard brain template (MNI152). Interrelationships between these components based on topographical overlap are displayed using relational graphs. Moreover, linkRbrain enables comparison of new experimental results with previous published works.Comparison with existing methodsPrevious tools and studies illustrate the opportunities of data mining across multiple tiers of neuroscience and genetic information. However, a global systematic approach is still missing to gather cognitive, topographical, and genetic knowledge in a common framework in order to facilitate their visualization, comparison, and integration.ConclusionsLinkRbrain is an efficient open-access tool that affords an integrative understanding of human brain function

The two intertwined rings corresponding to different type of temporal processing.

<p>The VSA ring (in blue) corresponds to high fidelity evoked processing and the PTF ring (in red) corresponds to more spontaneous processing more independent of input action potentials timing (from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115913#pone.0115913-Mesmoudi1" target="_blank">[3]</a>). Cortical regions sampled by the Allen Institute for Brain Sciences (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115913#pone.0115913-Hawrylycz1" target="_blank">[7]</a>) are represented by spheres colored like their respective rings. Points in sulci are not visible.</p

Map of the bootstrap ratios for the 161 genes, analyzed with DiCA, grouped per family and per class of neuronal function.

<p>In blue are represented genes with significant positive bootstrap ratios (<i>BT</i>>4.00) associated with the VSA ring and in red genes with significant negative bootstrap ratios (<i>BT</i><–4.00) associated with the PTF ring. For each family, extreme genes are identified. These genes are the most preferentially expressed in either VSA or PTF.</p

DiCA analysis: regions factor scores histogram.

<p>We plot the histogram of the factor score values–obtained for the 394 regions by the DiCA analysis–as a function of the number of regions <i>a priori</i> assigned to the VSA (blue) or the PTF (red) ring.</p