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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.14.516174v1?rss=1 Authors: Müller-Axt, C., Kauffmann, L., Eichner, C., von Kriegstein, K. Abstract: Developmental dyslexia (DD) is a reading disorder with a prevalence of 5-10%. Neuroscientific research has typically focused on explaining DD symptoms based on pathophysiological changes in the cerebral cortex. However, DD might also be associated with alterations in sensory thalami - central subcortical stations of sensory pathways. A post-mortem study on the visual sensory thalamus (lateral geniculate nucleus, LGN) showed histopathological changes in the magnocellular (M-LGN), but not in the parvocellular (P-LGN), subdivisions. M-LGN and P-LGN have different functional properties and belong to two different visual systems. Whether M-LGN alterations also exist in DD in-vivo is unclear. Also, the potential relevance of M-LGN alterations to DD symptoms is unknown. This lack of knowledge is partly due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans. Here, we employed recent advances in high-field 7 Tesla functional magnetic resonance imaging (fMRI) to map the M- and P-LGN in-vivo in DD adults (n=26) and matched controls (n=28). We show that (i) M-LGN responses differ between DD and control participants, (ii) these differences are more pronounced in male than in female DD participants, and (iii) M-LGN alterations predict a core symptom of DD in male DD participants only, i.e., rapid naming ability. Our results provide a first functional interpretation of M-LGN changes in DD and support DD theories that propose a direct relevance of sensory thalamus alterations for DD symptoms. In addition, the sex-specific behavioral relevance of M-LGN alterations within DD calls for taking sex differences into account when planning brain-based therapeutic interventions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.24.513555v1?rss=1 Authors: Velmeshev, D., Perez, Y., Yan, Z., Valencia, J. E., Castaneda-Castellanos, D. R., Schirmer, L., Mayer, S., Wick, B., Wang, S., Nowakowski, T. J., Paredes, M., Huang, E. J. J., Kriegstein, A. Abstract: Human cortical development involves birth, differentiation and maturation of a multitude of cellular lineages over the course of prenatal and postnatal life. Single-cell genomics provided insight into the molecular changes that underlie the development of early cortical lineages but has mostly been applied to the second trimester of prenatal human cortical development. Here, we utilize single-nucleus RNA sequencing to capture the development of the main human cortical lineages across prenatal and postnatal stages until adulthood and generate a comprehensive single-cell transcriptomic atlas of human cortical development. We collected more than 350,000 single-nucleus RNA-seq profiles from 108 tissue samples from 60 donors representing the second and third trimester of gestation, as well as neonatal, early and late postnatal stages of development. We identify lineage-specific developmental programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types and brain vasculature. Moreover, we discover sex- and region-specific developmental changes in each of these lineages. By intersecting our results with genetic risk factors for autism, we identify the cortical cell types and lineages most vulnerable to genetic insults that cause autism. We show that lineage-specific gene expression programs upregulated in female cells are especially enriched for the genetic risk factors of autism. Since these genes are expressed at lower levels in males during development, they may be more susceptible to heterozygous loss of function in ASD, providing a basis for the increased male to female ratio of autism incidence. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.24.513541v1?rss=1 Authors: Wang, L., Pang, K., Zhou, L., Cebrian-Silla, A., Gonzalez-Granero, S., Wang, S., Bi, Q., White, M. L., Ho, B., Li, J., Li, T., Perez, Y., Huang, E. J., Winkler, E. A., Paredes, M. F., Kovner, R., Sestan, N., Pollen, A. A., Liu, P., Li, J., Piao, X., Garcia-Verdugo, J. M., Alvarez-Buylla, A., Liu, Z., Kriegstein, A. R. Abstract: The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood. Here, we generated a cross-species proteomic map of synapse development in the human, macaque, and mouse neocortex. By tracking the changes of greater than 1,000 postsynaptic density (PSD) proteins from midgestation to adolescence, we found that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that the human PSD matures about three times slower than other species and contains higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of the RhoGEF signaling in human neurons delays the morphological maturation of dendritic spines and functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Together, our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
In his second talk, Kriegstein provides an overview of the use of cerebral organoids to study brain development and disease. Cerebral organoids are models that can be produced from induced pluripotent stem cells. Although organoids can contain the same broad categories of cell types found in the brain, organoids lack the structural, layer-like organization observed in the primary tissue. In addition, the gene expression profile is different between organoids and primary brain tissue. Nevertheless, although organoids do not reproduce all of the features of a developing human cortex, organoids can be a powerful model to study neuronal diseases and evolution, particularly when studying cells that cannot be found in animal models (e.g. oRG cells) or when scientists do not have access to primary brain tissue.
In his second talk, Kriegstein provides an overview of the use of cerebral organoids to study brain development and disease. Cerebral organoids are models that can be produced from induced pluripotent stem cells. Although organoids can contain the same broad categories of cell types found in the brain, organoids lack the structural, layer-like organization observed in the primary tissue. In addition, the gene expression profile is different between organoids and primary brain tissue. Nevertheless, although organoids do not reproduce all of the features of a developing human cortex, organoids can be a powerful model to study neuronal diseases and evolution, particularly when studying cells that cannot be found in animal models (e.g. oRG cells) or when scientists do not have access to primary brain tissue.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.14.250779v1?rss=1 Authors: Mueller-Axt, C., Eichner, C., Rusch, H., Kauffmann, L., Bazin, P.-L., Anwander, A., Morawski, M., von Kriegstein, K. Abstract: The human lateral geniculate nucleus (LGN) of the visual thalamus is a key subcortical processing site for visual information analysis. A non-invasive assessment of the LGN and its functionally and microstructurally distinct magnocellular (M) and parvocellular (P) subdivisions in-vivo in humans is challenging, because of its small size and location deep inside the brain. Here we tested whether recent advances in high-field structural quantitative MRI (qMRI) can enable MR-based mapping of human LGN subdivisions. We employed ultra-high resolution 7 Tesla qMRI of a post-mortem human LGN specimen and high-resolution 7 Tesla in-vivo qMRI in a large participant sample. We found that a quantitative assessment of the LGN and a differentiation of its subdivisions was possible based on microstructure-informed MR-contrast alone. In both the post-mortem and in-vivo qMRI data, we identified two components of shorter and longer longitudinal relaxation time (T1) within the LGN that coincided with the known anatomical locations of a dorsal P and a ventral M subdivision, respectively. Through a subsequent ground truth histological examination of the same post-mortem LGN specimen, we showed that the observed T1 contrast pertains to cyto- and myeloarchitectonic differences between LGN subdivisions. These differences were based on cell and myelin density, but not on iron content. Our qMRI-based mapping strategy overcomes shortcomings of previous fMRI-based mapping approaches. It paves the way for an in-depth understanding of the function and microstructure of the LGN in humans. It also enables investigations into the selective contributions of LGN subdivisions to human behavior in health and disease. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.14.095117v1?rss=1 Authors: Andrews, M. G., Subramanian, L., Kriegstein, A. R. Abstract: Outer radial glial (oRG) cells are a population of neural stem cells prevalent in the developing human cortex that contribute to its cellular diversity and evolutionary expansion. The mammalian Target of Rapamycin (mTOR) signaling pathway is active in human oRG cells. Mutations in mTOR pathway genes are linked to a variety of neurodevelopmental disorders and malformations of cortical development. We find that dysregulation of mTOR signaling specifically affects oRG cells, but not other progenitor types, by changing the actin cytoskeleton through the activity of the GTPase, CDC42. These effects change oRG cellular morphology, migration, and mitotic behavior. Thus, mTOR signaling can regulate the architecture of the developing human cortex by maintaining the cytoskeletal organization of oRG cells and the radial glia scaffold. Our study provides insight into how mTOR dysregulation may contribute to neurodevelopmental disease. Copy rights belong to original authors. Visit the link for more info
CARTA - Center for Academic Research and Training in Anthropogeny (Video)
UC San Francisco's Arnold Kriegstein addresses whether the Zika virus could someday be used to kill cancerous brain cells. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 32986]
CARTA - Center for Academic Research and Training in Anthropogeny (Audio)
UC San Francisco's Arnold Kriegstein addresses whether the Zika virus could someday be used to kill cancerous brain cells. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 32986]
The human brain is one of, if not the most important factor that distinguishes our species from all others. Three experts explore the use of stem cells in understanding the primate brain, genes that guided the evolution of the human brain, and the features that enabled the expansion of human neural characteristics. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32927]
The human brain is one of, if not the most important factor that distinguishes our species from all others. Three experts explore the use of stem cells in understanding the primate brain, genes that guided the evolution of the human brain, and the features that enabled the expansion of human neural characteristics. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32927]
The human brain is one of, if not the most important factor that distinguishes our species from all others. Three experts explore the use of stem cells in understanding the primate brain, genes that guided the evolution of the human brain, and the features that enabled the expansion of human neural characteristics. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32927]
CARTA - Center for Academic Research and Training in Anthropogeny (Video)
The human brain is one of, if not the most important factor that distinguishes our species from all others. Three experts explore the use of stem cells in understanding the primate brain, genes that guided the evolution of the human brain, and the features that enabled the expansion of human neural characteristics. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32927]
CARTA - Center for Academic Research and Training in Anthropogeny (Audio)
The human brain is one of, if not the most important factor that distinguishes our species from all others. Three experts explore the use of stem cells in understanding the primate brain, genes that guided the evolution of the human brain, and the features that enabled the expansion of human neural characteristics. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32927]
The human brain is one of, if not the most important factor that distinguishes our species from all others. Three experts explore the use of stem cells in understanding the primate brain, genes that guided the evolution of the human brain, and the features that enabled the expansion of human neural characteristics. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32927]
With the ongoing epidemic, Zika virus remains an ominous diagnosis for pregnant mothers. Since little was known about this disease prior to the outbreak, scientists are working quickly to close the research gap. Neurologist Arnold Kriegstein of the University of California, San Francisco recently identified a molecular bridge that could allow Zika to enter a baby’s brain from the bloodstream. Before, Zika’s use of this channel was mainly hypothetical. "But now, we do have access to the virus from Brazil, and we are actually doing these experiments. We’re taking these live cells and we’re exposing them to the virus." Kriegstein and his team will look at a variety of cell types, including developing neurons known as radial glial cells. "We’re also looking not just at the radial glial cells, which we expect will be infected, but other cell types, some of which we don’t expect to be infected. If we can understand the mechanism of how the virus is invading the brain, how it’s causing microcephaly that may provide some therapeutic targets that you could use to block the infection at some level."
This week were joined by Sami Kriegstein of the Los Angeles Music Video Festival (LAMVF) to break down the many layers of the new Jenny Lewis video, the many paint splatters of an amazing Garth Brooks 1994 video, and the many questions over how a Lamborghini taxi got into a Nicki Minaj video.
Home Leave (Grand Central Publishing) Chris Kriegstein is a man on the move, with a global career that catapults his family across North America, Europe, and Asia. For his wife, Elise, the hardship of chronic relocation is soothed by the allure of reinvention. Over the years, Elise shape-shifts: once a secretive Southern Baptist, she finds herself becoming a seasoned expat in Shanghai, an unapologetic adulterer in Thailand, and, finally, a renowned interior decorator in Madison. But it's the Kriegstein daughters, Leah and Sophie, who face the most tumult. Fiercely protective of each other-but also fiercely competitive-the two sisters long for stability in an ever-changing environment. With each new move, the girls find they can count on only one thing: the consoling, confounding presence of each other. When the family suffers an unimaginable loss, they can't help but wonder: Was it meant to be, or did one decision change their lives forever? And what does it mean when home is everywhere and nowhere at the same time? With humor and heart, Brittani Sonnenberg chases this wildly loveable family through the excitement and anguish of their adventures around the world. Praise for Home Leave “It's hard to believe that this astonishing novel is Brittani Sonnenberg's first--she writes about family with such wisdom, humor, and native daring. Here is Persephone's journey, undertaken by an entire family, the Kriegsteins, who ricochet through time zones, moving from Berlin to Singapore to Wisconsin to Shanghai to Atlanta, together and alone. Sonnenberg's prose is so vital and so enchanting that you will read this book in the dilated state of a world-traveler, with all of your senses wide open. Her family members are so well-drawn and complex that you'll close this book certain they exist.”—Karen Russell, author of Swamplandia! and Vampires in the Lemon Grove “Brittani Sonnenberg, like the best storytellers, shows us what we carry and what we leave behind as we travel across time zones (from America to Germany to Singapore), as we sit in airports, alone with the aloneness, as we love, live, grieve, and then try to live once more. Authentic, beautiful, bravely-told, Home Leave is alive with characters you want to protect and hold—characters you won't want to leave behind.”—Nami Mun, author of Miles from Nowhere “Home Leave is a remarkable debut, notable for the insightful intimacy of its characterization and a restless formal invention which perfectly evokes the uncertainties of expatriate life.”—Peter Ho Davies, author of The Welsh Girl Brittani Sonnenberg was raised across three continents and has worked as a journalist in Germany, China, and throughout Southeast Asia. A graduate of Harvard, she received her MFA in fiction from the University of Michigan. Her fiction has been published in The O'Henry Prize Stories 2008 as well as Ploughshares, Short Fiction, and Asymptote. Her nonfiction has appeared in Time, the Associated Press, the Minneapolis Star Tribune, and NPR Berlin. She has taught creative writing at the University of Michigan, Carleton College, and the University of Hong Kong. She is currently based in Berlin. Home Leave is her debut novel.
Sami Kriegstein, founder and director of the Los Angeles Music Video Festival, comes to Music Video Land to talk about the unique events at the festival, which will be held in Downtown Los Angeles on May 4th and 5th, 2012.