title: Generation of dense statistical connectomes from sparse morphological data.
abstract: 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 subcellular 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.
authors.affiliation: Computational Neuroanatomy Group, Max Planck Institute for Biological Cybernetics Tuebingen, Germany ; Graduate School of Neural Information Processing, University of Tuebingen Tuebingen, Germany ; Bernstein Center for Computational Neuroscience Tuebingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Egger
authors.affiliation: Department of Visual Data Analysis, Zuse Institute Berlin Berlin, Germany.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Dercksen
authors.affiliation: Computational Neuroanatomy Group, Max Planck Institute for Biological Cybernetics Tuebingen, Germany ; Graduate School of Neural Information Processing, University of Tuebingen Tuebingen, Germany ; Bernstein Center for Computational Neuroscience Tuebingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Udvary
authors.affiliation: Department of Visual Data Analysis, Zuse Institute Berlin Berlin, Germany.
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Hege
authors.affiliation: Computational Neuroanatomy Group, Max Planck Institute for Biological Cybernetics Tuebingen, Germany ; Bernstein Center for Computational Neuroscience Tuebingen, Germany ; Digital Neuroanatomy Group, Max Planck Florida Institute for Neuroscience Jupiter, FL, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Oberlaender
keywords: Peters' rule; axon; barrel cortex; cortical column; dendrite; thalamus