Trygve Brauns Leergaard

• Lillehaug, Sveinung; Yetman, Michael J.; Puchades, Maja; Checinska, Martyna; Kleven, Heidi; Jankowsky, Joanna L.; Bjaalie, Jan G. & Leergaard, Trygve B. (2019). Brain-wide distribution of reporter expression in five transgenic tetracycline-transactivator mouse lines. Scientific Data.  ISSN 2052-4463. . doi: https://doi.org/10.1038/sdata.2019.28
• Lillehaug, Sveinung; Yetman, Michael J.; Puchades, Maja; Checinska, Martyna; Kleven, Heidi; Jankowsky, Joanna L.; Bjaalie, Jan G. & Leergaard, Trygve B. (2019). Data Descriptor: Brain-wide distribution of reporter expression in five transgenic tetracyclinetransactivator mouse lines. Scientific Data.  ISSN 2052-4463.  6, s 1- 15 . doi: 10.1038/sdata.2019.28
• Puchades, Maja; Csúcs, Gergely; Ledergerber, Debora; Leergaard, Trygve B. & Bjaalie, Jan G. (2019). Spatial registration of serial microscopic brain images to three-dimensional reference atlases with the QuickNII tool. PLoS ONE.  ISSN 1932-6203.  14(5) . doi: 10.1371/journal.pone.0216796
• Bjerke, Ingvild Elise; Øvsthus, Martin; Andersson, Krister Andreas; Blixhavn, Camilla Hagen; Kleven, Heidi; Yates, Sharon Christine; Puchades, Maja; Bjaalie, Jan G. & Leergaard, Trygve B. (2018). Navigating the Murine Brain: Toward Best Practices for Determining and Documenting Neuroanatomical Locations in Experimental Studies. Frontiers in Neuroanatomy.  ISSN 1662-5129.  12 . doi: 10.3389/fnana.2018.00082
• Bjerke, Ingvild Elise; Øvsthus, Martin; Papp, Eszter Agnes; Yates, Sharon Christine; Silvestri, L; Fiorilli, J; Pennartz, CMA; Pavone, FS; Puchades, Maja; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2018). Data integration through brain atlasing: Human Brain Project tools and strategies. European psychiatry.  ISSN 0924-9338.  50, s 70- 76 . doi: 10.1016/j.eurpsy.2018.02.0
• Mughal, Awais; Zhang, Lili; Fayzullin, Artem; Server, Andrés; Li, Yuping; Wu, Yingxi; Glass, Rainer; Meling, Torstein Ragnar; Langmoen, Iver Arne; Leergaard, Trygve Brauns & Vik-Mo, Einar O. (2018). Patterns of Invasive Growth in Malignant Gliomas - The Hippocampus Emerges as an Invasion-Spared Brain Region. Neoplasia.  ISSN 1522-8002.  20(7), s 643- 656 . doi: 10.1016/j.neo.2018.04.001
• Stahl, Katja; Rahmani, Soulmaz; Prydz, Agnete; Skauli, Nadia; MacAulay, Nanna; Mylonakou, Maria-Niki; Torp, Reidun; Skare, Øivind; Berg, Torill; Leergaard, Trygve Brauns; Paulsen, Ragnhild Elisabeth; Ottersen, Ole Petter & Amiry-Moghaddam, Mahmood (2018). Targeted deletion of the aquaglyceroporin AQP9 is protective in a mouse model of Parkinson's disease. PLoS ONE.  ISSN 1932-6203.  13(3) . doi: 10.1371/journal.pone.0194896 Show summary

  More than 90% of the cases of Parkinson’s disease have unknown etiology. Gradual loss of dopaminergic neurons of substantia nigra is the main cause of morbidity in this disease. External factors such as environmental toxins are believed to play a role in the cell loss, although the cause of the selective vulnerability of dopaminergic neurons remains unknown. We have previously shown that aquaglyceroporin AQP9 is expressed in dopaminergic neurons and astrocytes of rodent brain. AQP9 is permeable to a broad spectrum of substrates including purines, pyrimidines, and lactate, in addition to water and glycerol. Here we test our hypothesis that AQP9 serves as an influx route for exogenous toxins and, hence, may contribute to the selective vulnerability of nigral dopaminergic (tyrosine hydroxylase-positive) neurons. Using Xenopus oocytes injected with Aqp9 cRNA, we show that AQP9 is permeable to the parkinsonogenic toxin 1-methyl-4-phenylpyridinium (MPP+). Stable expression of AQP9 in HEK cells increases their vulnerability to MPP+ and to arsenite—another parkinsonogenic toxin. Conversely, targeted deletion of Aqp9 in mice protects nigral dopaminergic neurons against MPP+ toxicity. A protective effect of Aqp9 deletion was demonstrated in organotypic slice cultures of mouse midbrain exposed to MPP+ in vitro and in mice subjected to intrastriatal injections of MPP+ in vivo. Seven days after intrastriatal MPP+ injections, the population of tyrosine hydroxylase-positive cells in substantia nigra is reduced by 48% in Aqp9 knockout mice compared with 67% in WT littermates. Our results show that AQP9 –selectively expressed in catecholaminergic neurons—is permeable to MPP+ and suggest that this aquaglyceroporin contributes to the selective vulnerability of nigral dopaminergic neurons by providing an entry route for parkinsonogenic toxins. To our knowledge this is the first evidence implicating a toxin permeable membrane channel in the pathophysiology of Parkinson’s disease.

• Blackstad, Jan Sigurd Beddari; Osen, Kirsten Kjelsberg; Scharfman, Helen E.; Storm-Mathisen, Jon; Blackstad, Theodor & Leergaard, Trygve Brauns (2016). Observations on hippocampal mossy cells in mink (Neovison vison) with special reference to dendrites ascending to the granular and molecular layers. Hippocampus.  ISSN 1050-9631.  26(2), s 229- 245 . doi: 10.1002/hipo.22518
• Papp, Eszter Agnes; Leergaard, Trygve Brauns; Csúcs, Gergely & Bjaalie, Jan G. (2016). Brain-wide mapping of axonal connections: Workflow for automated detection and spatial analysis of labeling in microscopic sections. Frontiers in Neuroinformatics.  ISSN 1662-5196.  10(11) . doi: 10.3389/fninf.2016.00011 Full text in Research Archive.
• Schubert, N; Axer, M; Schober, M; Huynh, A; Huysegoms, M; Palomero-Gallagher, N; Bjaalie, Jan G.; Leergaard, Trygve Brauns; Kirlangic, Mehmet E.; Amunts, K & Zilles, Karl (2016). 3D reconstructed cyto-, muscarinic M<sub>2</sub> receptor, and fiber architecture of the rat brain registered to the waxholm space atlas. Frontiers in Neuroanatomy.  ISSN 1662-5129.  10(MAY) . doi: 10.3389/fnana.2016.00051
• Yetman, Michael J.; Lillehaug, Sveinung; Bjaalie, Jan G.; Leergaard, Trygve Brauns & Jankowsky, Joanna L. (2016). Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex. Brain Structure and Function.  ISSN 1863-2653.  221(4), s 2231- 2249 . doi: 10.1007/s00429-015-1040-9
• Boccara, Charlotte Nina; Kjønigsen, Lisa Jannicke; Hammer, Ingvild Marie F.; Bjaalie, Jan G.; Leergaard, Trygve Brauns & Witter, Menno (2015). A three-plane architectonic atlas of the rat hippocampal region. Hippocampus.  ISSN 1050-9631.  25(7), s 838- 857 . doi: 10.1002/hipo.22407
• Kjønigsen, Lisa Jannicke; Lillehaug, Sveinung; Bjaalie, Jan G.; Witter, Menno & Leergaard, Trygve Brauns (2015). Waxholm Space atlas of the rat brain hippocampal region: Three-dimensional delineations based on magnetic resonance and diffusion tensor imaging. NeuroImage.  ISSN 1053-8119.  108, s 441- 449 . doi: 10.1016/j.neuroimage.2014.12.080 Full text in Research Archive.
• Papp, Eszter Agnes; Leergaard, Trygve Brauns; Calabrese, Evan; Johnson, G. Allan & Bjaalie, Jan G. (2015). Addendum to “Waxholm Space atlas of the Sprague Dawley rat brain” [NeuroImage 97 (2014) 374-386]. NeuroImage.  ISSN 1053-8119.  105, s 561- 562 . doi: 10.1016/j.neuroimage.2014.10.017
• Vårbakken, Kjartan; Steen, Harald; Samuelsen, Gunnar; Dahl, Hans A; Leergaard, Trygve Brauns & Stuge, Britt (2015). Primary functions of the quadratus femoris and obturator externus muscles indicated from lengths and moment arms measured in mobilized cadavers. Clinical Biomechanics.  ISSN 0268-0033.  30(3), s 231- 237 . doi: 10.1016/j.clinbiomech.2015.02.004
• Zakiewicz, Izabela Maria; Majka, Piotr; Wòjcik, Daniel K.; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2015). Three-Dimensional Histology Volume Reconstruction of Axonal Tract Tracing Data: Exploring Topographical Organization in Subcortical Projections from Rat Barrel Cortex. PLoS ONE.  ISSN 1932-6203.  10(9) . doi: 10.1371/journal.pone.0137571
• Lillehaug, Sveinung; Syverstad, Gry-Helen Enger; Nilsson, Lars; Bjaalie, Jan G.; Leergaard, Trygve Brauns & Torp, Reidun (2014). Brainwide distribution and variance of amyloid-beta deposits in tg-ArcSwe mice. Neurobiology of Aging.  ISSN 0197-4580.  35(3), s 556- 564 . doi: 10.1016/j.neurobiolaging.2013.09.013
• Nuruddin, Syed; Syverstad, Gry-Helen Enger; Lillehaug, Sveinung; Leergaard, Trygve Brauns; Nilsson, Lars; Ropstad, Erik; Krogenæs, Anette; Haraldsen, Ira Hebold & Torp, Reidun (2014). Elevated mRNA-Levels of Gonadotropin-Releasing Hormone and Its Receptor in Plaque-Bearing Alzheimer's Disease Transgenic Mice. PLoS ONE.  ISSN 1932-6203.  9(8) . doi: 10.1371/journal.pone.0103607
• Pandya, Abhilash D.; Leergaard, Trygve Brauns; Dissen, Erik; Haraldsen, Guttorm & Spurkland, Anne (2014). Expression of the T cell-specific adapter protein in human tissues. Scandinavian Journal of Immunology.  ISSN 0300-9475.  80(3), s 169- 179 . doi: 10.1111/sji.12199
• Papp, Eszter Agnes; Leergaard, Trygve Brauns; Calabrese, Evan; Johnson, G. Allan & Bjaalie, Jan G. (2014). Waxholm Space atlas of the Sprague Dawley rat brain. NeuroImage.  ISSN 1053-8119.  97, s 374- 386 . doi: 10.1016/j.neuroimage.2014.04.001
• Vårbakken, Kjartan; Steen, Harald; Samuelsen, Gunnar; Dahl, Hans A; Leergaard, Trygve Brauns; Nordsletten, Lars & Stuge, Britt (2014). Lengths of the external hip rotators in mobilized cadavers indicate the quadriceps coxa as a primary abductor and extensor of the flexed hip. Clinical Biomechanics.  ISSN 0268-0033.  29(7), s 794- 802 . doi: 10.1016/j.clinbiomech.2014.05.011
• Zakiewicz, Izabela Maria; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2014). Brain-wide map of efferent projections from rat barrel cortex. Frontiers in Neuroinformatics.  ISSN 1662-5196.  8 . doi: 10.3389/fninf.2014.00005
• Nagelhus, Erlend Arnulf; Amiry-Moghaddam, Mahmood; Bergersen, Linda Hildegard; Bjaalie, Jan G.; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve Brauns; Morth, Jens Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B & Tønjum, Tone (2013). The glia doctrine: Addressing the role of glial cells in healthy brain ageing. Mechanisms of Ageing and Development.  ISSN 0047-6374.  134(10), s 449- 459 . doi: 10.1016/j.mad.2013.10.001
• Stensrud, Mats Julius; Chaudhry, Farrukh Abbas; Leergaard, Trygve Brauns; Bjaalie, Jan G. & Gundersen, Vidar (2013). Vesicular glutamate transporter-3 in the rodent brain: Vesicular colocalization with vesicular -aminobutyric acid transporter. Journal of Comparative Neurology.  ISSN 0021-9967.  521(13), s 3042- 3056 . doi: 10.1002/cne.23331
• White, NS; Leergaard, Trygve Brauns; D'Arceuil, Helen; Bjaalie, Jan G. & Dale, AM (2013). Probing tissue microstructure with Restriction Spectrum Imaging: Histological and theoretical validation. Human Brain Mapping.  ISSN 1065-9471.  34(2), s 327- 346 . doi: 10.1002/hbm.21454
• Antonsen, Bjørnar Torske; Jiang, Yi; Veraart, Jelle; Qu, Hong; Nguyen, Huu Phuc; Sijbers, Jan; von Hörsten, Stephan; Johnson, G. Allan & Leergaard, Trygve Brauns (2012). Altered diffusion tensor imaging measurements in aged transgenic Huntington disease rats. Brain Structure and Function.  ISSN 1863-2653. . doi: 10.1007/s00429-012-0427-0
• Blockx, I; Verhoye, M; Van Audekerke, J; Bergwerf, I; Kane, John; Palacios, RDY; Veraart, J; Jeurissen, B; Raber, K; von Horsten, S; Ponsaerts, P; Sijbers, J; Leergaard, Trygve Brauns & Van der Linden, A (2012). Identification and characterization of Huntington related pathology: An in vivo DKI imaging study. NeuroImage.  ISSN 1053-8119.  63(2), s 653- 662 . doi: 10.1016/j.neuroimage.2012.06.032
• Leergaard, Trygve Brauns; Hilgetag, Claus C & Sporns, Olaf (2012). Mapping the connectome: multi-level analysis of brain connectivity. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/fninf.2012.00014
• Kjønigsen, Lisa Jannicke; Leergaard, Trygve Brauns; Witter, Menno & Bjaalie, Jan G. (2011). Digital atlas of anatomical subdivisions and boundaries of the rat hippocampal region. Frontiers in Neuroinformatics.  ISSN 1662-5196.  8(5) . doi: 10.3389/fninf.2011.00002
• Odeh, U. R. Francis; Leergaard, Trygve Brauns; Boy, J.; Schmidt, T.; Riess, O. & Bjaalie, Jan G. (2011). Atlas of transgenic Tet-Off Ca2+/calmodulin-dependent protein kinase II and prion protein promoter activity in the mouse brain. NeuroImage.  ISSN 1053-8119.  54(4), s 2603- 2611 . doi: 10.1016/j.neuroimage.2010.11.032
• Veraart, Jelle; Leergaard, Trygve Brauns; Antonsen, Bjørnar; Van Hecke, Wim; Blockx, Ines; Jeurissen, Ben; Jiang, Yi; Van der Linden, Annemie; Johnson, G. Allan; Verhoye, Marleen & Sijbers, Jan (2011). Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain. NeuroImage.  ISSN 1053-8119.  58(4), s 975- 983 . doi: 10.1016/j.neuroimage.2011.06.063
• Zakiewicz, Izabela Maria; Van Dongen, Yvette C; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2011). Workflow and Atlas System for Brain-Wide Mapping of Axonal Connectivity in Rat. PLoS ONE.  ISSN 1932-6203.  6(8) . doi: 10.1371/journal.pone.0022669
• Leergaard, Trygve Brauns; White, Nathan; De Crespigny, Alex; Bolstad, Ingeborg; D'Arceuil, Helen; Bjaalie, Jan G. & Dale, Anders M (2010). Quantitative Histological Validation of Diffusion MRI Fiber Orientation Distributions in the Rat Brain. PLoS ONE.  ISSN 1932-6203.  5(1) . doi: 10.1371/journal.pone.0008595
• Holmseth, Silvia; Scott, Heather A; Real, Katia; Lehre, Knut Petter Dæhlin; Leergaard, Trygve Brauns; Bjaalie, Jan G. & Danbolt, Niels Christian (2009). The concentrations and distributions of three C-terminal variants of the GLT1 (EAAT2; slc1a2) glutamate transporter protein in rat brain tissue suggest differential regulation. Neuroscience.  ISSN 0306-4522.  162(4), s 1055- 1071 . doi: 10.1016/j.neuroscience.2009.03.048
• Kjønigsen, Lisa Jannicke; Leergaard, Trygve Brauns; Moene, Ivar Andre; Witter, Menno P & Bjaalie, Jan G. (2009). Interactive atlas of the rat hippocampus integrating high-resolution histological images and boundary definitions. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.neuro.11.2009.08.013

View all works in Cristin

• Schlegel, Ulrike; Blixhavn, Camilla Hagen; Andersson, Krister Andreas; Yates, Sharon Christine; Øvsthus, Martin; Bjerke, Ingvild Elise; Kleven, Heidi; Groeneboom, Nicolaas Ervik; Puchades, Maja; Bjaalie, Jan G. & Leergaard, Trygve B. (2019). Integrating and analysing heterogeneous rodent neuroscience data using three-dimensional brain reference atlases. Show summary

  Achieving advances in the field of neuroscience with its rapidly growing number of published data requires integration across many scales and levels of investigation. Such integration is challenging due to the heterogeneous nature of the data, and the difficulty of comparing data from different studies. Key aspects include lack of standards for presentation of data and experimental parameters (metadata), and variable practices for assigning and reporting anatomical location in the brain. The EU Human Brain Project (HBP) is addressing these challenges by establishing an infrastructure of neuroinformatic tools and data curation services through which disparate neuroscience data can be shared, used and analysed. Three-dimensional (3D) open access brain reference atlases provide anatomical context for all the shared data, easing comparison and interpretation of findings. We here present HBP workflows for assigning metadata describing anatomical locations to different types of neuroscience data, and workflows for extracting, quantifying and co-visualizing morphological features from multiple datasets in 3D anatomical brain atlas viewers. We highlight the added value of mapping data to a common atlas framework in example studies, and demonstrate new analytic opportunities enabled by combining image analysis tools with information from a 3D brain reference atlas. The HBP now invites the community to use the new research infrastructure established.

• Andersson, Krister Andreas; Blixhavn, Camilla Hagen; Zehl, Lyuba; Markovic, Milica; Kleven, Heidi; Zafarnia, Sara; Köhnen, Stefan; Legouée, Elodie; Puchades, Maja; Schmid, Oliver; Davison, Andrew P.; Muller, Jeff; Dicksheid, Timo; Leergaard, Trygve B. & Bjaalie, Jan G. (2018). HBP Curation service: Share your data via the Neuroinformatics platform.
• Bjerke, Ingvild Elise; Øvsthus, Martin; Andersson, Krister Andreas; Bjaalie, Jan G. & Leergaard, Trygve B. (2018). Best practices for determining and documenting neuroanatomical locations in the rodent brain.
• Blixhavn, Camilla Hagen; Andersson, Krister; Øvsthus, Martin; Bjerke, Ingvild Elise; Kleven, Heidi; Puchades, Maja; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2018). Data integration through digital brain atlasing: Making diverse neuroscience data discoverable using Human Brain Project infrastructure.
• Papp, Eszter Agnes; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2018). Volumetric atlasing in the rodent brain: connecting experimental image data to standard anatomical space. Full text in Research Archive. Show summary

  A major challenge for understanding the brain in health and disease is related to combining information about the brain from many different sources. Spatial analysis and comparison of 2D and 3D brain images with the aim to discover new structural and functional features in the data requires mapping the images to a common anatomical space. For rodent models, widely used anatomical reference atlases have until recently been published in a book format that hinders effective comparison across images acquired at different angles and dimensions. The ambition of this study is to advance digital atlasing of the rodent brain towards a new generation of volumetric atlases that facilitate integration of whole-brain image data from multiple modalities. We present the first comprehensive anatomical reference atlas of the Sprague Dawley rat brain based on magnetic resonance imaging. To ensure interoperability with other atlases, we applied the Waxholm Space standard in the rat brain for the first time, and created a mapping against the widely used stereotaxic space. For connecting experimental data to the new reference atlas, we established standard anatomical landmarks for image registration across different levels of structural detail, and created a workflow for section to volume alignment and spatial analysis of brain-wide microscopic image series. Open access to the results of this work has enabled localization of signal in functional and structural image volumes, integration of 2D image series, and development of new atlases of various features of the brain.

• von Linstow, Christian Ulrich; Yates, Sharon Christine; Leergaard, Trygve B.; Plank, A-C; von Hörsten, S.; Puchades, Maja & Bjaalie, Jan G. (2018). Whole brain analysis of Huntingtin aggregates in the F344 transgenic rat model of Huntington’s disease.
• Yates, Sharon Christine; Puchades, Maja; kreshuk, anna; Kutra, Dominik; Leergaard, Trygve B.; Bjaalie, Jan G. & Groeneboom, Nicolaas (2018). HBP Analytic Workflow: from Microscopic Image Data to Extracted Features in Atlas Space.
• Zehl, Lyuba; Zafarnia, Sara; Köhnen, Stefan; Andersson, Krister Andreas; Markovic, Milica; Legouée, Elodie; Blixhavn, Camilla Hagen; Kleven, Heidi; Gui, Xiaoyun; Chervakov, Pavel; Schmid, Oliver; Bell, Simon; Gillespie, Tom; Abrams, Matthew; Davison, Andrew P.; Muller, Jeff; Leergaard, Trygve B.; Amunts, K; Bjaalie, Jan G. & Dicksheid, Timo (2018). Integrating neuroscientific data into a unified database: from individual experiments to a standardized metadata collection using the Human Brain Project Neuroinformatics Platform.
• Zehl, Lyuba; Zafarnia, Sara; Köhnen, Stefan; Andersson, Krister Andreas; Markovic, Milica; Legouée, Elodie; Blixhavn, Camilla Hagen; Kleven, Heidi; Gui, Xiaoyun; Chervakov, Pavel; Schmid, Oliver; Bell, Simon; Gillespie, Tom; Abrams, Matthew; Davison, Andrew P.; Muller, Jeff; Leergaard, Trygve B.; Amunts, K; Bjaalie, Jan G. & Dicksheid, Timo (2018). Integrating neuroscientific data into a unified database: from individual experiments to a standardized metadata collection using the Human Brain Project Neuroinformatics Platform.
• Øvsthus, Martin; Bjerke, Ingvild Elise; Yates, Sharon Christine; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2018). Mapping topographical organization in mouse brain subcortical axonal projections using Human Brain Project infrastructure.
• Andersson, Krister Andreas; Bell, Simon; Bjerke, Ingvild Elise; Øvsthus, Martin; Blixhavn, Camilla Hagen; Kleven, Heidi; Puchades, Maja; Suzen, M; Denker, Michael; Davison, A.; Grün, Sonja; Leprince, Y; Dickscheid, Timo; McMurtrie, C; Telefont, Martin; Muller, Jeff; Leergaard, Trygve B. & Bjaalie, Jan G. (2017). Submitting data and metadata through the HBP Data Workbench: Concepts, data flows, policies, and best practices.
• Andersson, Krister; Øvsthus, Martin; Bjerke, Ingvild Elise; Puchades, Maja; Telefont, Martin; Jeff, Muller; Dickscheid, Timo; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2017). Data integration through digital brain atlasing: Human Brain Project infrastructure. Show summary

  The Human Brain Project is building an ICT-based scientific research infrastructure that will permit researchers to advance our knowledge in the fields of neuroscience through data exploration, analytics and simulation at multiple levels of brain organization. Experimental neuroscience is connected to the infrastructure through systems for organizing and managing heterogeneous research data. These data systems are initially tested by data producing laboratories in the HBP, and will ultimately be opened for the community. HBP data curation services support users in elevating the level of data consistency and in the migration of data to the open domain. The starting point for research projects that will use HBP resources is the HBP Collaboratory, a rich collaborative workspace which is open to the community. The Collaboratory provides guidance and access to resources, including storage for data and a workbench for entering and organizing metadata. As a central element, the Collaboratory provides high-quality reference atlases of the rodent and human brain, together with appropriate tools and workflows that allow users to register data to the atlases for their study, and to perform initial analysis of data. It also links to important external data repositories and services. Here we present an overview of currently available reference atlases, tools and workflows. We exemplify the use of these resources in a range of neuroscience projects, ranging from brain-wide mapping of molecular level information to identification of precise location of electrophysiology recording sites. With coordinates corresponding to reference atlas space, harvested through the workflow, valuable metadata for future search and analysis of data are captured. Furthermore, with data aligned to reference atlases, analysis of the spatial distribution of events, labeled elements, and regions of interest in image material is strongly supported. Following registration to reference atlas, subsequent image processing and analysis steps delivers lists of extracted features corresponding to atlas structures, enabling quantitative regional analysis. We exemplify analytical workflows producing automated quantification and spatial analysis of labeling in series of histological section images from whole rodent brain. These and other atlas related workflows will be made available as HBP software services.

• Bjerke, Ingvild Elise; Andersson, Krister Andreas; Øvsthus, Martin; Puchades, Maja; Bjaalie, Jan G. & Leergaard, Trygve B. (2017). Navigating the rodent brain: Best practice recommendations for determining and documenting spatial location for neuroscience data.
• Bjerke, Ingvild Elise; Andersson, Krister; Øvsthus, Martin; Puchades, Maja; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2017). Determining and documenting the anatomical location of experimental neuroscience data: Best practice recommendations. Show summary

  Anatomical location is a key parameter for interpretation and comparison of neuroscientific data. Location is typically determined by looking up diagrams in anatomical reference atlases, communicated using anatomical terms, and shown in representative images. But the documentation provided varies considerably among scientific publications. Essential information about nomenclature and reference atlases, or criteria used to define boundaries of structures is often missing. This lack of accuracy limits the opportunities for comparing and integrating data from different publications, and could lead to failure in replicating scientific experiments. To clarify and address this challenge, we have investigated current practice for assigning and documenting anatomical location for different categories of experimental neuroscience data reported in > 120 articles investigating the rodent brain. Our findings show that the specificity and accuracy of anatomical documentation in most cases can be considerably improved with relatively simple procedures. We here suggest some general and method-specific recommendations for such improvements, and discuss how these steps may contribute to increase the accuracy of anatomical descriptions and data interpretation. We demonstrate how new three-dimensional rodent brain reference atlases, and associated software tools for spatial registration of brain image data to a common anatomical space, offer new opportunities for efficient integration and comparison of neuroscience data.

• Coello, Sebastian Christopher; Leergaard, Trygve B. & Bjaalie, Jan G. (2017). Tackling the normalization of 2-D rodent histology sections in a 3-D coordinate space.
• Coello, Sebastian Christopher; Leergaard, Trygve B. & Bjaalie, Jan G. (2017). Tackling the normalization of 2-D rodent histology sections in a 3-D coordinate space.
• Imad, Jala; Kleven, Heidi; Clascá, Francisco; Wennberg, Arvind Eirik; Osen, Kirsten Kjelsberg; Coello, Sebastian Christopher; Csúcs, Gergely; Papp, Eszter Agnes; Witter, Menno; Bjaalie, Jan G. & Leergaard, Trygve B. (2017). Enriching and adding detail to the Waxholm Space rat brain reference atlas.
• Imad, Jala; Osen, Kirsten Kjelsberg; Clascá, Francisco; Wennberg, Arvind E.; Coello, Sebastian Christopher; Csúcs, Gergely; Papp, Eszter Agnes; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2017). Enriching and Adding Detail to the Waxholm Space Rat Brain Reference Atlas. Show summary

  Brain reference atlases are important resources for assigning anatomical location to experimental data, and for planning and interpreting experimental results. Three-dimensional atlases can also serve as templates for spatial co-registration (integration) and comparison of different types of brain images. The Waxholm Space atlas of the rat brain is a public resource based on high resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data. It features a coordinate system based on internal landmarks (Waxholm Space) and delineations of so far 79 brain structures (Papp et al., Neuroimage 97:374-386, 2015; Kjonigsen et al., Neuroimage 108:441-449, 2015). The atlas is shared via the Neuroimaging Informatics Tools and Resources Clearinghouse (www.nitrc.org), and has since its release been widely adopted by the community. A limitation is, however, that detailed anatomical delineations of several major brain regions are missing. In some instances, delineations are not easily introduced due to low contrast in the underlying MRI / DTI templates, or complex features that are challenging to interpret in MRI / DTI data. To amend this, we have spatially registered images of serial histological sections stained for cyto-, chemo- and myeloarchitecture to the Waxholm Space rat brain template, and used these to aid the interpretation of boundaries of structures. We here outline our approach to defining brain structures in the Waxholm Space rat brain template, and present new delineations of the ascending auditory system, the thalamus, as well as several regions in the cerebral cortex and basal forebrain. The anatomical criteria underlying the delineations will be published, and the next version of the atlas delineations will be shared from www.nitrc.org.

• Leergaard, Trygve B. (2017). Building and using rodent brain reference atlases for integration of experimental data.
• Leprince, Y; Coello, Sebastian Christopher; Csúcs, Gergely; Chervakov, P; Darine, Dmitri Aleksandrovitsj; Øvsthus, Martin; Bjerke, Ingvild Elise; Yates, Sharon Christine; Puchades, Maja; Leergaard, Trygve B.; Dickscheid, Timo & Bjaalie, Jan G. (2017). Interactive tools for registering of 2D and 3D images to reference atlases.
• Puchades, Maja; Csúcs, Gergely; Checinska, Martyna; Øvsthus, Martin; Bjerke, Ingvild Elise; Andersson, Krister; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2017). Neuroinformatics tool and workflow for anchoring of serial histological images in rodent brain 3D space. Show summary

  Reference atlases of the brain are important tools for assigning location to data captured in neuroscience experiments. Spatial alignment of sectional images to reference atlases is, however, challenging to perform for several reasons. Manual approaches applied to large series of sectional images are time consuming and, moreover, histological sections are often cut at angles deviating from the principal anatomical planes presented in conventional reference atlases. Novel 3D reference atlases and accompanying tools provide new opportunities for rapid and accurate spatial registration and integration of data in common atlas space. We here present QuickNII which is new tools for use with the Waxholm Space atlas for the rat brain and the Allen Mouse brain atlas for the mouse brain, and a workflow that allows users to 1) interactively generate customized atlas images (slices of the 3D reference atlas) corresponding to the plane of sectioning of any experimental image series, 2) superimpose atlas images onto experimental images using affine transformations to match key anatomical landmarks, 3) propagate the transformations across a series of images, 4) assign spatial reference atlas coordinates to the experimental images, and 5) allow viewing and analysis of the experimental data integrated in the reference atlas. We exemplify the workflow and use of our methods with a range of experimental data from neuroanatomical and neurophysiological investigations.

• Puchades, Maja; Øvsthus, Martin; Bjerke, Ingvild Elise; Andersson, Krister; Csúcs, Gergely; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2017). Data integration through digital brain atlasing: semiautomatic spatial registration of serial histological images to rodent brain 3D reference atlases. Show summary

  Reference atlases of the brain are important tools for assigning location to data captured in neuroscience experiments. Spatial alignment of sectional images to reference atlases is, however, challenging to perform for several reasons. Manual approaches applied to large series of sectional images are time consuming and, moreover, histological sections are often cut at angles deviating from the principal anatomical planes presented in conventional reference atlases. Novel 3D reference atlases and accompanying tools provide new opportunities for rapid and accurate spatial registration and integration of data in common atlas space. We here present new tools for use with the Waxholm Space atlas for the rat brain and the Allen Mouse brain atlas, and workflow that allows users to 1) interactively generate customized atlas images (slices of the 3D reference atlas) corresponding to the plane of sectioning of any experimental image series, 2) superimpose atlas images onto experimental images using affine transformations to match key anatomical landmarks, 3) propagate the transformations across a series of images, 4) assign spatial reference atlas coordinates to the experimental images, and 5) allow viewing and analysis of the experimental data integrated in the reference atlas. We exemplify the work flow and use of our methods with a range of experimental data from neuroanatomical and neurophysiological investigations.

• Timonidis, Nestor; Bakker, Rembrandt; Øvsthus, Martin; Garcia-Amado, M; Porrero, C; Leergaard, Trygve B.; Clascá, Francisco & Tiesinga, Paul (2017). Towards predicting the full mesoconnectome based on data fusion.
• Yates, Sharon Christine; Puchades, Maja; Coello, Sebastian Christopher; Kreshuk, Anna; Hartlage-Rübsamen, Maike; Rossner, Steffen; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2017). Workflow for automated quantification and spatial analysis of labeling in microscoping rodent brain sections. Show summary

  Introduction: Automated analysis of series of microscopic images from rodent brains can to advantage be used in many neuroscience research projects. To this end, we present a workflow for the automated quantification and spatial analysis of labeling in large series of section images from rodent brain. As an example, we present the quantification of Alzheimer’s disease plaques across a whole mouse brain series immunohistochemically stained for the APP N-terminus (1D1). Method: As a first step, the whole brain image series was anchored to the Allen mouse brain atlas, using an in-house software tool (QuickNII), to produce accurate anatomical maps adapted to the orientation of the images. Subsequently, the section images were classified by use of the ilastik software tool, based on supervised random forest learning algorithms. The classifier relies on input from manual user annotations of selected training images and the image features intensity, edge and texture. In a separate process, the class corresponding to plaque staining was cleaned, to remove edge artifact and background noise. The classified images were subsequently analyzed on a whole brain and regional level with input from the atlas maps. Thereby, a list of individual plaque features (area, location, etc.), region level features (number of plaques, area of plaques, etc.) and whole brain features were derived, enabling quantitative regional analysis as a semi-automatic pipeline. Results: With limited user interaction, we identified and localized according to brain region, individual amyloid plaques across a whole brain image series (Figure 1). Further validation of the workflow is on-going.

• Yates, Sharon Christine; Puchades, Maja; Coello, Sebastian Christopher; Kreshuk, Anna; Hartlage-Rübsamen, Maike; Rossner, Steffen; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2017). Workflow for automated quantification and spatial analysis of labelling in microscoping rodent brain sections.
• Leergaard, Trygve B. (2016). Navigating the rodent brain: An anatomist’s guide to assigning location to brain image data.
• Puchades, Maja; Bjerke, Ingvild Elise; Øvsthus, Martin; Andersson, Krister; Csúcs, Gergely; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2016). Spatial registration of serial histological image data to reference brain atlases.
• Blackstad, Jan Sigurd Beddari; Osen, Kirsten Kjelsberg; Scharfman, HE; Storm-Mathisen, Jon; Blackstad, Theodor & Leergaard, Trygve Brauns (2015). Hippocampal mossy cells in mink (Neovison vison).
• Leergaard, Trygve Brauns (2015). Hjerneforskning i den digitale tidsalder: Fremtidens hjerneatlas.
• Puchades, Maja Amedjkouh; Darine, Dmitri Aleksandrovitsj; Csúcs, Gergely; Lillehaug, Sveinung; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2015). Feeding rodent brain data to computational models through HBP spatial atlas templates and knowledge graph portal.
• Schubert, N; Axer, M; Graessel, D; Schober, M; Huynh, A; Huysegoms, M; Palomero-Gallagher, N; Bjaalie, Jan G.; Leergaard, Trygve Brauns; Zilles, K & Amunts, K (2015). 3D reconstructed fiber-, cyto- and receptorarchitecture of the rat brain transferred into the Waxholm Space atlas.
• Bjaalie, Jan G. & Leergaard, Trygve Brauns (2014). Neuroscience in the information ages: Brain atlasing goes digital. META.  ISSN 1890-2987.  (2), s 14- 17
• Leergaard, Trygve Brauns (2014). Navigating the rodent brain by digital atlasing.
• Leergaard, Trygve Brauns & Bjaalie, Jan G. (2014). Infrastructure for digital atlasing of mouse and rat brain: Rodent Brain WorkBench.
• Leergaard, Trygve Brauns; Coello, Christopher; Papp, Eszter Agnes; Ragan, Tim & Bjaalie, Jan G. (2014). Registration of serial two-photon data to rodent brain Waxholm Space. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.fninf.2014.18.00059
• Leergaard, Trygve Brauns; Coello, Christopher; Papp, Eszter Agnes; Ragan, Tim & Bjaalie, Jan G. (2014). Registration of serial two-photon data to rodent brain Waxholm Space.
• Leergaard, Trygve Brauns; Lillehaug, Sveinung; Papp, Eszter Agnes; Coello, Christopher; Ragan, Tim & Bjaalie, Jan G. (2014). Waxholm Space atlas template enriched with serial two-photon and histological data.
• Leergaard, Trygve Brauns; Lillehaug, Sveinung; Yetman, Michael J.; Jankowsky, Joanna L. & Bjaalie, Jan G. (2014). Interactive brainwide atlas of tetracycline responsive trans-activator promoter mouse lines.
• Leergaard, Trygve Brauns; Yetman, Michael J.; Lillehaug, Sveinung; Bjaalie, Jan G. & Jankowsky, Joanna L. (2014). Transgene expression in the neuropsin tTA driver line is not restricted to the entorhinal cortex.
• Papp, Eszter Agnes; Leergaard, Trygve Brauns; Csucs, Gergely; Darine, Dmitri Aleksandrovitsj & Bjaalie, Jan G. (2014). Workflow for integration and analysis of histological data in rodent brain Waxholm Space.
• Papp, Eszter Agnes; Leergaard, Trygve Brauns; Csucs, Gergely; Darine, Dmitri Aleksandrovitsj & Bjaalie, Jan G. (2014). Workflow for integration and analysis of histological data in rodent brain Waxholm Space. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.fninf.2014.18.00060
• Bjaalie, Jan G.; Papp, Eszter Agnes; Kjonigsen, LJ; Johnson, GA; Witter, Menno & Leergaard, Trygve Brauns (2013). Waxholm Space Atlas of the rat brain with detailed hippocampal subdivisions. Show summary

  Volumetric brain atlases are typically built on top of template data sets acquired with Magnetic Resonance Imaging. A relatively high level of structural details is provided combined with the advantage of allowing the entire brain to be viewed interactively in any plane. With appropriate tools for interactive viewing, volumetric atlases are useful for planning of experiments and data analysis by registration of other data sets to the atlas. We provide a volumetric atlas of the rat brain based on ex vivo MRI anatomical (T2*) images with 39 μm isotropic voxels and diffusion tensor imaging (DTI) volumes with 78 μm isotropic voxels acquired from an 80 day old male Sprague-Dawley rat. The atlas covers 83 anatomical structures (areas, nuclei, regions, and fiber tracts) across the brain. The structures were delineated using ITK-SNAP software based on multiple types of image contrasts and anatomical reference information. White matter structures were readily distinguished from grey matter, and some structural differences could also be observed within gray matter. Delineations were aided by information from classical 2D atlases and collections of histological images from brains of comparable animals, and delineation criteria were defined for all structures. Cyto- and chemoarchitectonic features from an online 2D histological atlas (Kjonigsen et al., Front Neuroinform. 2011) were used for delineation of 16 structures in the hippocampal region. The atlas and the underlying MRI and DTI image volumes are to be made open access through the INCF Software Center. Spatial reference is provided by Waxholm Space, a standard atlas space recently defined by the International Neuroinformatics Coordinating Facility (INCF). Waxholm Space connects the atlas to a growing infrastructure of interoperable resources and services for multi-level data integration and analysis across reference spaces.

• Syverstad, Gry-Helen Enger; Lillehaug, Sveinung; Nilsson, Lars N. G.; Bjaalie, Jan G.; Leergaard, Trygve B. & Torp, Reidun (2013). Spatial distribution and variance of amyloid-beta load in middle-aged transgenic Alzheimer’s disease mice with both the Artic and Swedish AβPP mutations.
• Syverstad, Gry-Helen Enger; Nuruddin, Syed; Lillehaug, Sveinung; Leergaard, Trygve B.; Haraldsen, Ira Hebold & Torp, Reidun (2013). Targeting gonadotroping-releasing hormone in Alzheimer’s disease.
• Papp, Eszter Agnes; Leergaard, Trygve Brauns; Johnson, G. Allan & Bjaalie, Jan G. (2012). First generation Waxholm atlas of the Sprague-Dawley rat brain.
• Kjønigsen, Lisa Jannicke; Leergaard, Trygve Brauns; Witter, Menno & Bjaalie, Jan G. (2011). Three-dimensional atlas framework for mapping of projections from the entorhinal cortex to the hippocampal formation in rat. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.fninf.2011.08.00129
• Leergaard, Trygve Brauns (2011). Interpreting morphological substrates of diffusion MRI: Histological validation approaches and 3D rat brain atlasing.
• Moene, Ivar Andre; Darine, Dmitri Aleksandrovitsj; Ramachandran, Muthuraja; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2011). Rodent Brain Navigator: database and atlas system for microscopy and imaging data. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.fninf.2011.08.00159
• Papp, Eszter Agnes; Leergaard, Trygve B.; Jiang, Yi; Johnson, G. Allan & Bjaalie, Jan G. (2011). Multimodal digital atlas of the rat brain: data integration in a high resolution volumetric template. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.fninf.2011.08.00013
• Zakiewicz, Izabela Maria; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2011). Neuroinformatics web applications for 3-D analysis of brain connectivity: anatomical organization of subcortical projections from whisker and forelimb regions of the rat somatosensory cortex. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.fninf.2011.08.00060
• Antonsen, Bjørnar T; Jiang, Yi; Veraart, J; Van Dongen, Yvette C; Qu, Hong; Urbach, Yvonne K; Raber, Kerstin; Nguyen, Huu P.; Sijbers, J; von Hörsten, Stephan; Johnson, G A & Leergaard, Trygve Brauns (2010). Altered ex vivo diffusion MRI in basal ganglia of transgenic Huntington's disease rats.
• Kjønigsen, Lisa Jannicke; Leergaard, Trygve Brauns; Witter, Menno & Bjaalie, Jan Gunnar (2010). Interactive atlas of the rat hippocampus: assigning location to experimental histological data using cyto- and chemoarchitectonical boundary definitions and a linked image repository.
• Leergaard, Trygve Brauns (2010). Morphological phenotyping of rodent transgenic models of brain disease.
• Van Dongen, Yvette C; Molvær, Arnold JN; van Camp, Nadja; Blockx, I; Urbach, Yvonne K; Raber, Kerstin; Van Der Linden, A; von Hörsten, Stephan; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2010). Structural analysis of the cortico-basal ganglia connectivity in a transgenic rat model of Huntington's disease.
• Van Dongen, Yvette C; Molvær, Arnold John Ngugi; Van Camp, Nadja; Blockx, I; Urbach, Yvonne K; Raber, Kerstin; Van Der Linden, A; von Hörsten, Stephan; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2010). Reduced corticostriatal but intact striatofugal projections in transgenic rat model of Huntington's disease.
• Zakiewicz, Izabela Maria; Van Dongen, Yvette C; Leergaard, Trygve Brauns & Bjaalie, Jan G. (2010). Workflow and database system for brain-wide mapping of axonal connectivity in rat.
• Melsom, Caroline B.; Leergaard, Trygve Brauns; Darine, Dmitri Aleksandrovitsj; Dale, Anders M & Bjaalie, Jan G. (2009). Three-dimensional visualization of rat corticofugal axonal trajectories using manganese enhanced magnetic resonance imaging and digital atlasing. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.neuro.11.2009.08.027
• White, Nathan; Leergaard, Trygve Brauns; De Crespigny, Alex & Dale, Anders M. (2009). A New Method for Resolving Complex Tissue Microstructures in Diffusion MRI.
• Antonsen, Bjørnar; Jiang, Yi; Qu, Hong; Van Dongen, Yvette C; Urbach, Yvonne K.; Raber, Kerstin; Nguyen, Huu P.; von Hörsten, Stephan; Johnson, G. Allan & Leergaard, Trygve Brauns (2009). Altered diffusion MRI in the basal ganglia of transgenic rat model of Huntington’s disease.
• Boy, J.; Schmidt, T.; Bottcher, M; Schumann, U.; Leergaard, Trygve Brauns; Odeh, Francis; Wolburg, H; Nuber, S.; Holzmann, C.; Schmitt, I; Zimmermann, F; Bjaalie, Jan G. & Riess, O. (2009). Clinical symptoms in SCA3 are reversible: a study using an inducible mouse model of SCA3. Journal of Neurochemistry.  ISSN 0022-3042.  110, s 97- 97
• Kjønigsen, Lisa Jannicke; Leergaard, Trygve Brauns; Bjaalie, Jan G. & Witter, Menno P (2009). Interactive Resource for Cytoarchitectonic Delineation of the Rat Hippocampus Formation and Associated Parahippocampal Cortex.
• Leergaard, Trygve Brauns (2009). Evaluation of neural network changes in transgenic rat model of Huntington’s disease: Preliminary findings.
• Leergaard, Trygve Brauns (2009). Oppdagelsesreiser i hjernens nervenettverk.
• Leergaard, Trygve Brauns; Antonsen, Bjørnar; Qu, Hong; Van Dongen, Yvette C; Jiang, Yi; Raber, Kerstin; Urbach, Yvonne; Nguyen, Huu P.; von Hörsten, Stephan & Johnson, G. Allan (2009). Ex vivo diffusion MRI measurements in symptomatic HD transgenic rats.
• Odeh, U. R. Francis; Schmidt, T.; Boy, J.; Moene, Ivar Andre; Riess, O.; Bjaalie, Jan G. & Leergaard, Trygve Brauns (2009). Interactive mouse brain atlas of tetracycline-responsive calmodulin-dependent protein kinase II- and prion protein promoter expression. Frontiers in Neuroinformatics.  ISSN 1662-5196. . doi: 10.3389/conf.neuro.11.2009.08.012

View all works in Cristin