Motivation Structural connectomics supports understanding aspects of neuronal dynamics and brain functions. Conducting metastudies of tract-tracing publications is one option to generate connectome databases by collating neuronal connectivity data. Meanwhile, it is a common practice that the neuronal connections and their attributes of such retrospective data collations are extracted from tract-tracing publications manually by experts. As the description of tract-tracing results is often not clear-cut and the documentation of interregional connections is not standardized, the extraction of connectivity data from tract-tracing publications could be complex. This might entail that different experts interpret such non-standardized descriptions of neuronal connections from the same publication in variable ways. Hitherto, no investigation is available that determines the variability of extracted connectivity information from original tract-tracing publications. A relatively large variability of connectivity information could produce significant misconstructions of adjacency matrices with faults in network and graph analyzes. The objective of this study is to investigate the inter-rater and inter-observation variability of tract-tracing-based documentations of neuronal connections. To demonstrate the variability of neuronal connections, data of 16 publications which describe neuronal connections of subregions of the hypothalamus have been assessed by way of example. Results A workflow is proposed that allows detecting variability of connectivity at different steps of data processing in connectome metastudies. Variability between three blinded experts was found by comparing the connection information in a sample of 16 publications that describe tract-tracing-based neuronal connections in the hypothalamus. Furthermore, observation scores, matrix visualizations of discrepant connections and weight variations in adjacency matrices are analyzed. Availability The resulting data and software are available at http://neuroviisas.med.uni-rostock.de/neuroviisas.shtml

The basal ganglia of the laboratory rat consist of a few core regions that are specifically interconnected by efferents and afferents of the central nervous system. In nearly 800 reports of tract-tracing investigations the connectivity of the basal ganglia is documented. The readout of connectivity data and the collation of all the connections of these reports in a database allows to generate a connectome. The collation, curation and analysis of such a huge amount of connectivity data is a great challenge and has not been performed before (Bohland et al. PloS One 4:e7200, 2009) in large connectomics projects based on meta-analysis of tract-tracing studies. Here, the basal ganglia connectome of the rat has been generated and analyzed using the consistent cross-platform and generic framework neuroVIISAS. Several advances of this connectome meta-study have been made: the collation of laterality data, the network-analysis of connectivity strengths and the assignment of regions to a hierarchically organized terminology. The basal ganglia connectome offers differences in contralateral connectivity of motoric regions in contrast to other regions. A modularity analysis of the weighted and directed connectome produced a specific grouping of regions. This result indicates a correlation of structural and functional subsystems. As a new finding, significant reciprocal connections of specific network motifs in this connectome were detected. All three principal basal ganglia pathways (direct, indirect, hyperdirect) could be determined in the connectome. By identifying these pathways it was found that there exist many further equivalent pathways possessing the same length and mean connectivity weight as the principal pathways. Based on the connectome data it is unknown why an excitation pattern may prefer principal rather than other equivalent pathways. In addition to these new findings the local graph-theoretical features of regions of the connectome have been determined. By performing graph theoretical analyses it turns out that beside the caudate putamen further regions like the mesencephalic reticular formation, amygdaloid complex and ventral tegmental area are important nodes in the basal ganglia connectome. The connectome data of this meta-study of tract-tracing reports of the basal ganglia are available for further network studies, the integration into neocortical connectomes and further extensive investigations of the basal ganglia dynamics in population simulations.

Event Abstract Back to Event Central and peripheral monosynaptic, polysynaptic and collaterals connectivity in the rat Oliver Schmitt1*, Peter Eipert1, Rene Hoffmann2, Paulinne Morawska1, Ann-Christin Klünker1, Jennifer Meinhardt1, Felix Lessmann1, Julia Beier1, Kanar Kadir1, Adrian Karnitzki1, Jörg Jenssen1, Lena Kuch1, Linda Sellner1 and Andreas Wree1 1 University of Rostock, Anatomy, Germany 2 University of Rostock, Mathematics, Germany Most stereotaxic tract-tracing studies were performed in the laboratory rat. Therefore, the most comprehensive knowledge of central and peripheral nervous system connectivity is available for this tetrapode vertebrate. The rat connectome project is a long term metastudy that aims to collate all connections described in peer reviewed articles documenting neuronal connections detected by stereotaxic tract-tracing techniques in juvenile and adult normal rats (non-genetically and non-experimentally modified). So far, connections of 4300 reports have been collated and currated by experts in neuroanatomy. These data, have been imported in the generic framework neuroVIISAS (http://neuroviisas.med.uni-rostock.de/) for advanced connectome analysis and simulation. To combine the different granularities of the collated connections, an extensive hierarchy of parts of the nervous system of the rat was created, containing all the regions participating in the imported connections and distiguishing the different hemispheric parts. This hierarchical approach and the extend of collated data is unique and allows the most precise connectome analysis on different levels of granularity with regard to ipsi-, contra-, bi- and unilateral specifications of connections. The hierarchical terminology is directly related to brain regions defined in different stereoteaxic atlases of the rat central nervous system. 2D- and 3D-atlas data are directly available and are used to visualize connectivity spatially. In addition 223 single neuron parameters of the Senselab database (http://neuroelectro.org) have been related to types of neurons used in neuron models implemented in NEST. In neuroVIISAS an interface to NEST (http://www.nest-initiative.org) is available that allows to use all NEST neuron models and moduls of the simulation engine in combination with real world connectivity and neuron parameters. To complete the number of critical parameters of realistic simulations we will present first results of a high-throughput-high-resolution identification of single cells of a terabyte virtual-slide dataset. For the first time, the rat connectome project also includes collateral connections from multi-tracer reports as well as pathways from transneuronal tract-tracing publications. This different type of connectivity data can be efficiently seperated from the conventional monosynaptic non-collateral one and integrated in population simulations. Currently the connectome consists of 232688 ipsi- and contralateral weighted (connection strength) and directed connections, completed by 2253 transneuronal pathways and 605 collateral sources. In conclusion, a nearly complete collation of consistent multiscale connectivity data of a whole nervous system of the rat is available (http://neuroviisas.med.uni-rostock.de). The laboratory rat is a well known vertebrate of which a huge amount of neuroscientific data exist. Such an outstanding source of connectivity, neuroanatomical, neurophysiological and behavioral data could be a promising starting point for multimodal large scale simulations in order to understand cognition and behavior of a complex vertebrate nervous systems. Keywords: connectomics, digital atlasing, rat nervous system, virtual slides, computational neuroscience, cell detection Conference: Neuroinformatics 2014, Leiden, Netherlands, 25 Aug - 27 Aug, 2014. Presentation Type: Demo, to be considered for oral presentation Topic: Digital atlasing Citation: Schmitt O, Eipert P, Hoffmann R, Morawska P, Klünker A, Meinhardt J, Lessmann F, Beier J, Kadir K, Karnitzki A, Jenssen J, Kuch L, Sellner L and Wree A (2014). Central and peripheral monosynaptic, polysynaptic and collaterals connectivity in the rat. Front. Neuroinform. Conference Abstract: Neuroinformatics 2014. doi: 10.3389/conf.fninf.2014.18.00058 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Apr 2014; Published Online: 04 Jun 2014. * Correspondence: Prof. Oliver Schmitt, University of Rostock, Anatomy, Rostock, 18057, Germany, schmitt@med.uni-rostock.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Oliver Schmitt Peter Eipert Rene Hoffmann Paulinne Morawska Ann-Christin Klünker Jennifer Meinhardt Felix Lessmann Julia Beier Kanar Kadir Adrian Karnitzki Jörg Jenssen Lena Kuch Linda Sellner Andreas Wree Google Oliver Schmitt Peter Eipert Rene Hoffmann Paulinne Morawska Ann-Christin Klünker Jennifer Meinhardt Felix Lessmann Julia Beier Kanar Kadir Adrian Karnitzki Jörg Jenssen Lena Kuch Linda Sellner Andreas Wree Google Scholar Oliver Schmitt Peter Eipert Rene Hoffmann Paulinne Morawska Ann-Christin Klünker Jennifer Meinhardt Felix Lessmann Julia Beier Kanar Kadir Adrian Karnitzki Jörg Jenssen Lena Kuch Linda Sellner Andreas Wree PubMed Oliver Schmitt Peter Eipert Rene Hoffmann Paulinne Morawska Ann-Christin Klünker Jennifer Meinhardt Felix Lessmann Julia Beier Kanar Kadir Adrian Karnitzki Jörg Jenssen Lena Kuch Linda Sellner Andreas Wree Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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