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 - 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 - 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 - 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 - 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 -