Workflow and Atlas System for Brain-Wide Mapping of Axonal Connectivity in Rat

Abstract

Detailed knowledge about the anatomical organization of axonal connections is important for understanding normal functions of brain systems and disease-related dysfunctions. Such connectivity data are typically generated in neuroanatomical tract-tracing experiments in which specific axonal connections are visualized in histological sections. Since journal publications typically only accommodate restricted data descriptions and example images, literature search is a cumbersome way to retrieve overviews of brain connectivity. To explore more efficient ways of mapping, analyzing, and sharing detailed axonal connectivity data from the rodent brain, we have implemented a workflow for data production and developed an atlas system tailored for online presentation of axonal tracing data. The system is available online through the Rodent Brain WorkBench (www.rbwb.org; Whole Brain Connectivity Atlas) and holds experimental metadata and high-resolution images of histological sections from experiments in which axonal tracers were injected in the primary somatosensory cortex. We here present the workflow and the data system, and exemplify how the online image repository can be used to map different aspects of the brain-wide connectivity of the rat primary somatosensory cortex, including not only presence of connections but also morphology, densities, and spatial organization. The accuracy of the approach is validated by comparing results generated with our system with findings reported in previous publications. The present study is a contribution to a systematic mapping of rodent brain connections and represents a starting point for further large-scale mapping efforts.

Brain-wide map of efferent projections from rat barrel cortex

“…The positions of the injection site centers were inferred from histological analyses of anatomical landmarks and cytochrome oxidase staining patterns (Zakiewicz et al, 2011). Inspection of sections stained for cytochrome oxidase revealed that the injections into S1 barrel cortex involved both barrels (D2, D3 or D5) and adjacent septa.…”

CoCoMac 2.0 and the future of tract-tracing databases

“…The rat connectivity component of the rodent brain workbench (Zakiewicz et al, 2011), providing public access to raw tract-tracing images, registered to a common atlas space.…”

Mapping the connectome: Multi-level analysis of brain connectivity

“…But despite the numerous connectivity studies conducted through many decades we are still far from achieving comprehensive descriptions of the connectome across all these levels. There is increasing awareness that new neuroinformatics tools and strategies are needed to achieve the goal of compiling the brain's connectome, and that any such effort will require systematic, large-scale approaches (Bohland et al, 2009;Akil et al, 2011;Zakiewicz et al, 2011;Van Essen and Ugurbil, 2012).…”

“…Further, curated databases may collaborate more closely with field experts, in order to preserve the multi-faceted neuroanatomical knowledge acquired in many experimental labs over several decades (where knowledge is currently threatened by the upcoming retirement of many of the "traditional" anatomists), or new experimental efforts may be started for the systematic, "industrial" brain connectivity gathering in rodent models (Bohland et al, 2009;Zakiewicz et al, 2011).…”