TY - GEN A1 - Dercksen, Vincent J. A1 - Hege, Hans-Christian A1 - Oberlaender, Marcel T1 - The Filament Editor: An Interactive Software Environment for Visualization, Proof-Editing and Analysis of 3D Neuron Morphology N2 - Neuroanatomical analysis, such as classification of cell types, depends on reliable reconstruction of large numbers of complete 3D dendrite and axon morphologies. At present, the majority of neuron reconstructions are obtained from preparations in a single tissue slice in vitro, thus suffering from cut off dendrites and, more dramatically, cut off axons. In general, axons can innervate volumes of several cubic millimeters and may reach path lengths of tens of centimeters. Thus, their complete reconstruction requires in vivo labeling, histological sectioning and imaging of large fields of view. Unfortunately, anisotropic background conditions across such large tissue volumes, as well as faintly labeled thin neurites, result in incomplete or erroneous automated tracings and even lead experts to make annotation errors during manual reconstructions. Consequently, tracing reliability renders the major bottleneck for reconstructing complete 3D neuron morphologies. Here, we present a novel set of tools, integrated into a software environment named ‘Filament Editor’, for creating reliable neuron tracings from sparsely labeled in vivo datasets. The Filament Editor allows for simultaneous visualization of complex neuronal tracings and image data in a 3D viewer, proof-editing of neuronal tracings, alignment and interconnection across sections, and morphometric analysis in relation to 3D anatomical reference structures. We illustrate the functionality of the Filament Editor on the example of in vivo labeled axons and demonstrate that for the exemplary dataset the final tracing results after proof-editing are independent of the expertise of the human operator. T3 - ZIB-Report - 13-75 Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-43157 SN - 1438-0064 ER - TY - JOUR A1 - Dercksen, Vincent J. A1 - Hege, Hans-Christian A1 - Oberlaender, Marcel T1 - The Filament Editor: An Interactive Software Environment for Visualization, Proof-Editing and Analysis of 3D Neuron Morphology JF - NeuroInformatics Y1 - 2014 U6 - https://doi.org/10.1007/s12021-013-9213-2 VL - 12 IS - 2 SP - 325 EP - 339 PB - Springer US ER - TY - GEN A1 - Egger, Robert A1 - Dercksen, Vincent J. A1 - Kock, Christiaan P.J. A1 - Oberlaender, Marcel ED - Cuntz, Hermann ED - Remme, Michiel W.H. ED - Torben-Nielsen, Benjamin T1 - Reverse Engineering the 3D Structure and Sensory-Evoked Signal Flow of Rat Vibrissal Cortex T2 - The Computing Dendrite Y1 - 2014 U6 - https://doi.org/10.1007/978-1-4614-8094-5_8 VL - 11 SP - 127 EP - 145 PB - Springer CY - New York ER - TY - JOUR A1 - Landau, Itamar D. A1 - Egger, Robert A1 - Dercksen, Vincent J. A1 - Oberlaender, Marcel A1 - Sompolinsky, Haim T1 - The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in Cortical Networks JF - Neuron N2 - Models of cortical dynamics often assume a homogeneous connectivity structure. However, we show that heterogeneous input connectivity can prevent the dynamic balance between excitation and inhibition, a hallmark of cortical dynamics, and yield unrealistically sparse and temporally regular firing. Anatomically based estimates of the connectivity of layer 4 (L4) rat barrel cortex and numerical simulations of this circuit indicate that the local network possesses substantial heterogeneity in input connectivity, sufficient to disrupt excitation-inhibition balance. We show that homeostatic plasticity in inhibitory synapses can align the functional connectivity to compensate for structural heterogeneity. Alternatively, spike-frequency adaptation can give rise to a novel state in which local firing rates adjust dynamically so that adaptation currents and synaptic inputs are balanced. This theory is supported by simulations of L4 barrel cortex during spontaneous and stimulus-evoked conditions. Our study shows how synaptic and cellular mechanisms yield fluctuation-driven dynamics despite structural heterogeneity in cortical circuits. Y1 - 2016 U6 - https://doi.org/10.1016/j.neuron.2016.10.027 VL - 92 IS - 5 SP - 1106 EP - 1121 ER - TY - JOUR A1 - Udvary, Daniel A1 - Harth, Philipp A1 - Macke, Jakob H. A1 - Hege, Hans-Christian A1 - de Kock, Christiaan P. J. A1 - Sakmann, Bert A1 - Oberlaender, Marcel T1 - A Theory for the Emergence of Neocortical Network Architecture JF - BioRxiv Y1 - 2020 U6 - https://doi.org/https://doi.org/10.1101/2020.11.13.381087 ER - TY - JOUR A1 - Kleinfeld, David A1 - Bharioke, Arjun A1 - Blinder, Pablo A1 - Bock, David A1 - Briggman, Kevin A1 - Chklovskii, Dmitri A1 - Denk, Winfried A1 - Helmstaedter, Moritz A1 - Kaufhold, John A1 - Lee, Wei-Chung A1 - Meyer, Hanno A1 - Micheva, Kristina A1 - Oberlaender, Marcel A1 - Prohaska, Steffen A1 - Reid, R. A1 - Smith, Stephen A1 - Takemura, Shinya A1 - Tsai, Philbert A1 - Sakmann, Bert T1 - Large-scale automated histology in the pursuit of connectomes JF - Journal of Neuroscience Y1 - 2011 UR - http://www.zib.de/prohaska/docs/Kleinfeld_JNS_Connectomes_2011.pdf U6 - https://doi.org/10.1523/JNEUROSCI.4077-11.2011 VL - 31 IS - 45 SP - 16125 EP - 16138 ER - TY - JOUR A1 - Lang, Stefan A1 - Dercksen, Vincent J. A1 - Sakmann, Bert A1 - Oberlaender, Marcel T1 - Simulation of signal flow in 3D reconstructions of an anatomically realistic neural network in rat vibrissal cortex JF - Neural Networks Y1 - 2011 U6 - https://doi.org/doi:10.1016/j.neunet.2011.06.013 VL - 24 IS - 9 SP - 998 EP - 1011 ER - TY - GEN A1 - Dercksen, Vincent J. A1 - Oberlaender, Marcel A1 - Sakmann, Bert A1 - Hege, Hans-Christian T1 - Light Microscopy-Based Reconstruction and Interactive Structural Analysis of Cortical Neural Networks T2 - BioVis 2011 Abstracts, 1st IEEE Symposium on Biological Data Visualization Y1 - 2011 ER - TY - GEN A1 - Dercksen, Vincent J. A1 - Oberlaender, Marcel A1 - Sakmann, Bert A1 - Hege, Hans-Christian ED - Linsen, Lars ED - Hagen, Hans ED - Hamann, Bernd ED - Hege, Hans-Christian T1 - Interactive Visualization – a Key Prerequisite for Reconstruction of Anatomically Realistic Neural Networks T2 - Visualization in Medicine and Life Sciences II Y1 - 2012 UR - http://www.zib.de/visual/publications/sources/src-2012/DercksenVMLS2012web.pdf SP - 27 EP - 44 PB - Springer, Berlin ER - TY - CHAP A1 - Dercksen, Vincent J. A1 - Egger, Robert A1 - Hege, Hans-Christian A1 - Oberlaender, Marcel T1 - Synaptic Connectivity in Anatomically Realistic Neural Networks: Modeling and Visual Analysis T2 - Eurographics Workshop on Visual Computing for Biology and Medicine (VCBM) Y1 - 2012 U6 - https://doi.org/10.2312/VCBM/VCBM12/017-024 SP - 17 EP - 24 CY - Norrköping, Sweden ER - TY - JOUR A1 - Oberlaender, Marcel A1 - de Kock, Christiaan P. J. A1 - Bruno, Randy M. A1 - Ramirez, Alejandro A1 - Meyer, Hanno A1 - Dercksen, Vincent J. A1 - Helmstaedter, Moritz A1 - Sakmann, Bert T1 - Cell Type-Specific Three-Dimensional Structure of Thalamocortical Circuits in a Column of Rat Vibrissal Cortex JF - Cerebral Cortex Y1 - 2012 U6 - https://doi.org/doi:10.1093/cercor/bhr317 VL - 22 IS - 10 SP - 2375 EP - 2391 ER - TY - GEN A1 - Oberlaender, Marcel A1 - Dercksen, Vincent J. A1 - Lang, Stefan A1 - Sakmann, Bert T1 - 3D mapping of synaptic connections within “in silico” microcircuits of full compartmental neurons in extended networks on the example of VPM axons projecting into S1 of rats. T2 - Conference Abstract, Neuroinformatics Y1 - 2009 U6 - https://doi.org/10.3389/conf.neuro.11.2009.08.092 ER - TY - GEN A1 - Oberlaender, Marcel A1 - Bruno, Randy M. A1 - de Kock, Christiaan P. J. A1 - Meyer, Hanno A1 - Dercksen, Vincent J. A1 - Sakmann, Bert T1 - 3D distribution and sub-cellular organization of thalamocortical VPM synapses for individual excitatory neuronal cell types in rat barrel cortex T2 - Conference Abstract No. 173.19/Y35, 39th Annual Meeting of the Society for Neuroscience (SfN) Y1 - 2009 ER - TY - GEN A1 - Oberlaender, Marcel A1 - Dercksen, Vincent J. A1 - Broser, Philip J. A1 - Bruno, Randy M. A1 - Sakmann, Bert T1 - NeuroMorph and NeuroCount: Automated tools for fast and objective acquisition of neuronal morphology for quantitative structural analysis T2 - Frontiers in Neuroinformatics. Conference Abstract: Neuroinformatics Y1 - 2008 U6 - https://doi.org/10.3389/conf.neuro.11.2008.01.065 ER - TY - CHAP A1 - Dercksen, Vincent J. A1 - Weber, Britta A1 - Günther, David A1 - Oberlaender, Marcel A1 - Prohaska, Steffen A1 - Hege, Hans-Christian T1 - Automatic alignment of stacks of filament data T2 - Proc. IEEE International Symposium on Biomedical Imaging Y1 - 2009 SP - 971 EP - 974 PB - IEEE press CY - Boston, USA ER - TY - JOUR A1 - Oberlaender, Marcel A1 - Dercksen, Vincent J. A1 - Egger, Robert A1 - Gensel, Maria A1 - Sakmann, Bert A1 - Hege, Hans-Christian T1 - Automated three-dimensional detection and counting of neuron somata JF - Journal of Neuroscience Methods Y1 - 2009 U6 - https://doi.org/10.1016/j.jneumeth.2009.03.008 VL - 180 IS - 1 SP - 147 EP - 160 ER - TY - JOUR A1 - Egger, Robert A1 - Dercksen, Vincent J. A1 - Udvary, Daniel A1 - Hege, Hans-Christian A1 - Oberlaender, Marcel T1 - Generation of dense statistical connectomes from sparse morphological data JF - Frontiers in Neuroanatomy Y1 - 2014 U6 - https://doi.org/10.3389/fnana.2014.00129 VL - 8 IS - 129 ER - TY - GEN A1 - Egger, Robert A1 - Dercksen, Vincent J. A1 - Udvary, Daniel A1 - Hege, Hans-Christian A1 - Oberlaender, Marcel T1 - Generation of dense statistical connectomes from sparse morphological data N2 - Sensory-evoked signal flow, at cellular and network levels, is primarily determined by the synaptic wiring of the underlying neuronal circuitry. Measurements of synaptic innervation, connection probabilities and sub-cellular organization of synaptic inputs are thus among the most active fields of research in contemporary neuroscience. Methods to measure these quantities range from electrophysiological recordings over reconstructions of dendrite-axon overlap at light-microscopic levels to dense circuit reconstructions of small volumes at electron-microscopic resolution. However, quantitative and complete measurements at subcellular resolution and mesoscopic scales to obtain all local and long-range synaptic in/outputs for any neuron within an entire brain region are beyond present methodological limits. Here, we present a novel concept, implemented within an interactive software environment called NeuroNet, which allows (i) integration of sparsely sampled (sub)cellular morphological data into an accurate anatomical reference frame of the brain region(s) of interest, (ii) up-scaling to generate an average dense model of the neuronal circuitry within the respective brain region(s) and (iii) statistical measurements of synaptic innervation between all neurons within the model. We illustrate our approach by generating a dense average model of the entire rat vibrissal cortex, providing the required anatomical data, and illustrate how to measure synaptic innervation statistically. Comparing our results with data from paired recordings in vitro and in vivo, as well as with reconstructions of synaptic contact sites at light- and electron-microscopic levels, we find that our in silico measurements are in line with previous results. T3 - ZIB-Report - 14-43 KW - 3D neural network KW - Dense connectome KW - Reconstruction Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-53075 SN - 1438-0064 ER - TY - CHAP A1 - Harth, Philipp A1 - Bast, Arco A1 - Troidl, Jakob A1 - Meulemeester, Bjorge A1 - Pfister, Hanspeter A1 - Beyer, Johanna A1 - Oberlaender, Marcel A1 - Hege, Hans-Christian A1 - Baum, Daniel T1 - Rapid Prototyping for Coordinated Views of Multi-scale Spatial and Abstract Data: A Grammar-based Approach T2 - Eurographics Workshop on Visual Computing for Biology and Medicine (VCBM) N2 - Visualization grammars are gaining popularity as they allow visualization specialists and experienced users to quickly create static and interactive views. Existing grammars, however, mostly focus on abstract views, ignoring three-dimensional (3D) views, which are very important in fields such as natural sciences. We propose a generalized interaction grammar for the problem of coordinating heterogeneous view types, such as standard charts (e.g., based on Vega-Lite) and 3D anatomical views. An important aspect of our web-based framework is that user interactions with data items at various levels of detail can be systematically integrated and used to control the overall layout of the application workspace. With the help of a concise JSON-based specification of the intended workflow, we can handle complex interactive visual analysis scenarios. This enables rapid prototyping and iterative refinement of the visual analysis tool in collaboration with domain experts. We illustrate the usefulness of our framework in two real-world case studies from the field of neuroscience. Since the logic of the presented grammar-based approach for handling interactions between heterogeneous web-based views is free of any application specifics, it can also serve as a template for applications beyond biological research. Y1 - 2023 U6 - https://doi.org/10.2312/vcbm.20231218 ER - TY - JOUR A1 - Harth, Philipp A1 - Udvary, Daniel A1 - Boelts, Jan A1 - Baum, Daniel A1 - Macke, Jakob H. A1 - Hege, Hans-Christian A1 - Oberlaender, Marcel T1 - Dissecting origins of wiring specificity in dense cortical connectomes JF - bioRxiv N2 - Wiring specificity in the cortex is observed across scales from the subcellular to the network level. It describes the deviations of connectivity patterns from those expected in randomly connected networks. Understanding the origins of wiring specificity in neural networks remains difficult as a variety of generative mechanisms could have contributed to the observed connectome. To take a step forward, we propose a generative modeling framework that operates directly on dense connectome data as provided by saturated reconstructions of neural tissue. The computational framework allows testing different assumptions of synaptic specificity while accounting for anatomical constraints posed by neuron morphology, which is a known confounding source of wiring specificity. We evaluated the framework on dense reconstructions of the mouse visual and the human temporal cortex. Our template model incorporates assumptions of synaptic specificity based on cell type, single-cell identity, and subcellular compartment. Combinations of these assumptions were sufficient to model various connectivity patterns that are indicative of wiring specificity. Moreover, the identified synaptic specificity parameters showed interesting similarities between both datasets, motivating further analysis of wiring specificity across species. Y1 - 2024 U6 - https://doi.org/10.1101/2024.12.14.628490 ER - TY - JOUR A1 - Boelts, Jan A1 - Harth, Philipp A1 - Gao, Richard A1 - Udvary, Daniel A1 - Yanez, Felipe A1 - Baum, Daniel A1 - Hege, Hans-Christian A1 - Oberlaender, Marcel A1 - Macke, Jakob H. T1 - Simulation-based inference for efficient identification of generative models in computational connectomics JF - PLOS Computational Biology N2 - Recent advances in connectomics research enable the acquisition of increasing amounts of data about the connectivity patterns of neurons. How can we use this wealth of data to efficiently derive and test hypotheses about the principles underlying these patterns? A common approach is to simulate neuronal networks using a hypothesized wiring rule in a generative model and to compare the resulting synthetic data with empirical data. However, most wiring rules have at least some free parameters, and identifying parameters that reproduce empirical data can be challenging as it often requires manual parameter tuning. Here, we propose to use simulation-based Bayesian inference (SBI) to address this challenge. Rather than optimizing a fixed wiring rule to fit the empirical data, SBI considers many parametrizations of a rule and performs Bayesian inference to identify the parameters that are compatible with the data. It uses simulated data from multiple candidate wiring rule parameters and relies on machine learning methods to estimate a probability distribution (the 'posterior distribution over parameters conditioned on the data') that characterizes all data-compatible parameters. We demonstrate how to apply SBI in computational connectomics by inferring the parameters of wiring rules in an in silico model of the rat barrel cortex, given in vivo connectivity measurements. SBI identifies a wide range of wiring rule parameters that reproduce the measurements. We show how access to the posterior distribution over all data-compatible parameters allows us to analyze their relationship, revealing biologically plausible parameter interactions and enabling experimentally testable predictions. We further show how SBI can be applied to wiring rules at different spatial scales to quantitatively rule out invalid wiring hypotheses. Our approach is applicable to a wide range of generative models used in connectomics, providing a quantitative and efficient way to constrain model parameters with empirical connectivity data. Y1 - 2023 U6 - https://doi.org/10.1371/journal.pcbi.1011406 VL - 19 IS - 9 ER - TY - JOUR A1 - Boelts, Jan A1 - Harth, Philipp A1 - Gao, Richard A1 - Udvary, Daniel A1 - Yanez, Felipe A1 - Baum, Daniel A1 - Hege, Hans-Christian A1 - Oberlaender, Marcel A1 - Macke, Jakob H T1 - Simulation-based inference for efficient identification of generative models in connectomics JF - bioRxiv N2 - Recent advances in connectomics research enable the acquisition of increasing amounts of data about the connectivity patterns of neurons. How can we use this wealth of data to efficiently derive and test hypotheses about the principles underlying these patterns? A common approach is to simulate neural networks using a hypothesized wiring rule in a generative model and to compare the resulting synthetic data with empirical data. However, most wiring rules have at least some free parameters and identifying parameters that reproduce empirical data can be challenging as it often requires manual parameter tuning. Here, we propose to use simulation-based Bayesian inference (SBI) to address this challenge. Rather than optimizing a single rule to fit the empirical data, SBI considers many parametrizations of a wiring rule and performs Bayesian inference to identify the parameters that are compatible with the data. It uses simulated data from multiple candidate wiring rules and relies on machine learning methods to estimate a probability distribution (the `posterior distribution over rule parameters conditioned on the data') that characterizes all data-compatible rules. We demonstrate how to apply SBI in connectomics by inferring the parameters of wiring rules in an in silico model of the rat barrel cortex, given in vivo connectivity measurements. SBI identifies a wide range of wiring rule parameters that reproduce the measurements. We show how access to the posterior distribution over all data-compatible parameters allows us to analyze their relationship, revealing biologically plausible parameter interactions and enabling experimentally testable predictions. We further show how SBI can be applied to wiring rules at different spatial scales to quantitatively rule out invalid wiring hypotheses. Our approach is applicable to a wide range of generative models used in connectomics, providing a quantitative and efficient way to constrain model parameters with empirical connectivity data. Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-89890 ER - TY - CHAP A1 - Harth, Philipp A1 - Vohra, Sumit A1 - Udvary, Daniel A1 - Oberlaender, Marcel A1 - Hege, Hans-Christian A1 - Baum, Daniel T1 - A Stratification Matrix Viewer for Analysis of Neural Network Data T2 - Eurographics Workshop on Visual Computing for Biology and Medicine (VCBM) N2 - The analysis of brain networks is central to neurobiological research. In this context the following tasks often arise: (1) understand the cellular composition of a reconstructed neural tissue volume to determine the nodes of the brain network; (2) quantify connectivity features statistically; and (3) compare these to predictions of mathematical models. We present a framework for interactive, visually supported accomplishment of these tasks. Its central component, the stratification matrix viewer, allows users to visualize the distribution of cellular and/or connectional properties of neurons at different levels of aggregation. We demonstrate its use in four case studies analyzing neural network data from the rat barrel cortex and human temporal cortex. Y1 - 2022 U6 - https://doi.org/10.2312/vcbm.20221194 CY - Vienna, Austria ER - TY - JOUR A1 - Udvary, Daniel A1 - Harth, Philipp A1 - Macke, Jakob H. A1 - Hege, Hans-Christian A1 - de Kock, Christiaan P. J. A1 - Sakmann, Bert A1 - Oberlaender, Marcel T1 - The Impact of Neuron Morphology on Cortical Network Architecture JF - Cell Reports N2 - The neurons in the cerebral cortex are not randomly interconnected. This specificity in wiring can result from synapse formation mechanisms that connect neurons depending on their electrical activity and genetically defined identity. Here, we report that the morphological properties of the neurons provide an additional prominent source by which wiring specificity emerges in cortical networks. This morphologically determined wiring specificity reflects similarities between the neurons’ axo-dendritic projections patterns, the packing density and cellular diversity of the neuropil. The higher these three factors are the more recurrent is the topology of the network. Conversely, the lower these factors are the more feedforward is the network’s topology. These principles predict the empirically observed occurrences of clusters of synapses, cell type-specific connectivity patterns, and nonrandom network motifs. Thus, we demonstrate that wiring specificity emerges in the cerebral cortex at subcellular, cellular and network scales from the specific morphological properties of its neuronal constituents. Y1 - 2022 U6 - https://doi.org/10.1016/j.celrep.2022.110677 VL - 39 IS - 2 ER -