title: Whole-brain 3D mapping of human neural transplant innervation.
abstract: While transplantation represents a key tool for assessing in vivo functionality of neural stem cells and their suitability for neural repair, little is known about the integration of grafted neurons into the host brain circuitry. Rabies virus-based retrograde tracing has developed into a powerful approach for visualizing synaptically connected neurons. Here, we combine this technique with light sheet fluorescence microscopy (LSFM) to visualize transplanted cells and connected host neurons in whole-mouse brain preparations. Combined with co-registration of high-precision three-dimensional magnetic resonance imaging (3D MRI) reference data sets, this approach enables precise anatomical allocation of the host input neurons. Our data show that the same neural donor cell population grafted into different brain regions receives highly orthotopic input. These findings indicate that transplant connectivity is largely dictated by the circuitry of the target region and depict rabies-based transsynaptic tracing and LSFM as efficient tools for comprehensive assessment of host-donor cell innervation.
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.|Life&Brain GmbH, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Doerr
authors.affiliation: Life&Brain GmbH, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.|Department of Epileptology, Functional Neuroconnectomics Group, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Martin Karl
authors.initials: MK
authors.lastname: Schwarz
authors.affiliation: Max Planck Institute for Metabolism Research, In-vivo-NMR Laboratory, Gleuelerstrasse 50, 50931 Cologne, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wiedermann
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Leinhaas
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Jakobs
authors.affiliation: Institute of Physical and Theoretical Chemistry, University of Bonn, Wegeler Strasse 12, 53115 Bonn, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schloen
authors.affiliation: Department of Epileptology, Functional Neuroconnectomics Group, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Inna
authors.initials: I
authors.lastname: Schwarz
authors.affiliation: Max Planck Institute for Metabolism Research, In-vivo-NMR Laboratory, Gleuelerstrasse 50, 50931 Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Diedenhofen
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Nils Christian
authors.initials: NC
authors.lastname: Braun
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Koch
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, 60064 North Chicago, Illinois, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Peterson
authors.affiliation: Institute of Physical and Theoretical Chemistry, University of Bonn, Wegeler Strasse 12, 53115 Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kubitscheck
authors.affiliation: Max Planck Institute for Metabolism Research, In-vivo-NMR Laboratory, Gleuelerstrasse 50, 50931 Cologne, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.|Life&Brain GmbH, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
mesh_terms: D000818:Animals; D001921:Brain; D001931:Brain Mapping; D002454:Cell Differentiation / Q000502:physiology; D005822:Genetic Vectors; D006801:Humans; D007395:Interneurons; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D058953:Neural Stem Cells / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000637:transplantation*; D011820:Rabies virus / Q000502:physiology