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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.25.534233v1?rss=1 Authors: Virga, D. M., Hamilton, S., Osei, B., Morgan, A., Zamponi, E., Park, N. J., Hewitt, V. L., Zhang, D., Gonzalez, K. C., Bloss, E., Polleux, F., Lewis, T. L. Abstract: Neuronal mitochondria play important roles beyond ATP generation, including Ca2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly in the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a new activity-dependent molecular mechanism underlying the extreme subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise regulation of mitochondria fission/fusion balance. 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/2023.03.01.530630v1?rss=1 Authors: Libe-Philippot, B., Iwata, R., Recupero, A. J., Wierda, K., Ditkowska, M., Gaspariunaite, V., Vermaercke, B., Peze-Heidsieck, E., Remans, D., Charrier, C., Polleux, F., Vanderhaeghen, P. Abstract: Human-specific (HS) genes are potential drivers of brain evolution, but their impact on human neuron development and disease remains unclear. Here we studied HS genes SRGAP2B/C in human cortical projection neurons (CPNs) in vivo, using xenotransplantation in the mouse cortex. Downregulation of SRGAP2B/C in human CPNs greatly accelerated synaptic development, indicating their requirement for human-specific synaptic neoteny. SRGAP2B/C acted by downregulating their ancestral paralog SRGAP2A, thereby upregulating postsynaptic levels of SYNGAP1, a major intellectual deficiency/autism spectrum disorder (ID/ASD) gene. Combinatorial genetic invalidation revealed that the tempo of synaptogenesis is set by a balance between SRGAP2A and SYNGAP1, which in human CPNs is tipped towards neoteny by SRGAP2B/C. Our results demonstrate that HS genes can modify the phenotypic expression of ID/ASD mutations through regulation of synaptic neoteny. 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/2020.10.14.338681v1?rss=1 Authors: Turner, N. L., Macrina, T., Bae, J. A., Yang, R., Wilson, A. M., Schneider-Mizell, C., Lee, K., Lu, R., Wu, J., Bodor, A. L., Bleckert, A. A., Brittain, D., Froudarakis, E., Dorkenwald, S., Collman, F., Kemnitz, N., Ih, D., Silversmith, W. M., Zung, J., Zlateski, A., Tartavull, I., Yu, S.-c., Popovych, S., Mu, S., Wong, W., Jordan, C. S., Castro, M., Buchanan, J., Bumbarger, D. J., Takeno, M., Torres, R., Mahalingam, G., Elabbady, L., Li, Y., Cobos, E., Zhou, P., Suckow, S., Becker, L., Paninski, L., Polleux, F., Reimer, J., Tolias, A. S., Reid, R. C., Macarico da Costa, N., Seung, H. S. Abstract: We present a semi-automated reconstruction of L2/3 mouse primary visual cortex from 3 million cubic microns of electron microscopic images, including pyramidal and inhibitory neurons, astrocytes, microglia, oligodendrocytes and precursors, pericytes, vasculature, mitochondria, and synapses. Visual responses of a subset of pyramidal cells are included. The data are being made publicly available, along with tools for programmatic and 3D interactive access. The density of synaptic inputs onto inhibitory neurons varies across cell classes and compartments. We uncover a compartment-specific correlation between mitochondrial coverage and synapse density. Frequencies of connectivity motifs in the graph of pyramidal cells are predicted quite accurately from node degrees using the configuration model of random graphs. Cells receiving more connections from nearby cells exhibit stronger and more reliable visual responses. These example findings illustrate the resource's utility for relating structure and function of cortical circuits as well as for neuronal cell biology. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.30.229724v1?rss=1 Authors: Pilaz, L.-J., Joshi, K., Liu, J., Tsunekawa, Y., Alsina, F., Sethi, S., Suzuki, I., Vanderhaeghen, P., Polleux, F., Silver, D. Abstract: mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in highly polarized and elongated cells. These features are especially prominent in radial glial cells (RGCs), which serve as neural and glial precursors of the developing cerebral cortex, and scaffolds for migrating neurons. Yet the mechanisms by which distinct sub-cellular compartments of RGCs accomplish their diverse functions are poorly understood. Here, we demonstrate that subcellular RNA localization and translation of the RhoGAP Arhgap11a controls RGC morphology and mediates cortical cytoarchitecture. Arhgap11a mRNA and protein exhibit conserved localization to RGC basal structures in mice and humans, conferred by a 5'UTR cis-element. Proper RGC morphology relies upon active Arhgap11a mRNA transport and localization to basal structures, where ARHGAP11A is locally synthesized. Thus, RhoA activity is spatially and acutely activated via local translation in RGCs to promote neuron positioning and cortical cytoarchitecture. Altogether, our study demonstrates that mRNA localization and local translation mediate compartmentalization of neural progenitor functions to control brain development. Copy rights belong to original authors. Visit the link for more info
CARTA - Center for Academic Research and Training in Anthropogeny (Video)
New insights into the significance of the emergence of a human-specific gene on brain evolution. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32975]
CARTA - Center for Academic Research and Training in Anthropogeny (Audio)
New insights into the significance of the emergence of a human-specific gene on brain evolution. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32975]
New insights into the significance of the emergence of a human-specific gene on brain evolution. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32975]
New insights into the significance of the emergence of a human-specific gene on brain evolution. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32975]
CARTA - Center for Academic Research and Training in Anthropogeny (Video)
The way cells differentiate to eventually form the human brain and all the unique connections that make us human is ultimately the result of processes forged in evolution. Three experts share their investigations into characteristics of the human genome and its changes throughout evolution that make us human. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32928]
CARTA - Center for Academic Research and Training in Anthropogeny (Audio)
The way cells differentiate to eventually form the human brain and all the unique connections that make us human is ultimately the result of processes forged in evolution. Three experts share their investigations into characteristics of the human genome and its changes throughout evolution that make us human. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32928]
The way cells differentiate to eventually form the human brain and all the unique connections that make us human is ultimately the result of processes forged in evolution. Three experts share their investigations into characteristics of the human genome and its changes throughout evolution that make us human. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32928]
The way cells differentiate to eventually form the human brain and all the unique connections that make us human is ultimately the result of processes forged in evolution. Three experts share their investigations into characteristics of the human genome and its changes throughout evolution that make us human. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 32928]
On this episode of Brain Matters, Matt and Dr. Franck Polleux (Professor, Department of Neuroscience at Columbia University and the Zuckerman Mind Brain Behavior Institute) cover a lot of ground. Franck talks about his work as a graduate student and the topics his lab is working on now. The Polleux lab is studying topics like neural progeneration, mitochondria in dendrites of neurons, and what makes the human brain special. This is an episode you won't want to miss.
On this episode of Brain Matters, Matt and Dr. Franck Polleux (Professor, Department of Neuroscience at Columbia University and the Zuckerman Mind Brain Behavior Institute) cover a lot of ground. Franck talks about his work as a graduate student and the topics his lab is working on now. The Polleux lab is studying topics like neural progeneration, mitochondria in dendrites of neurons, and what makes the human brain special. This is an episode you won't want to miss.