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 - 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 -