Morphotype-specific calcium signaling in human microglia

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Key functions of Ca 2+ signaling in rodent microglia include monitoring the brain state or the surrounding neuronal activity and sensing the danger or damage in their vicinity. Microglial Ca 2+ dyshomeostasis is a disease hallmark in many mouse models of neurological disorders but the Ca 2+ signal properties of human microglia remain unknown. Using a newly developed toolbox, we analyzed in situ Ca 2+ signaling of decades-old human cortical microglia. The data revealed marked compartmentalization of Ca 2+ signals, with signal properties differing across the compartments and resident morphotypes. The basal Ca 2+ levels were low in ramified and high in ameboid microglia. The fraction of cells with ongoing Ca 2+ signaling, the fraction and the amplitude of process Ca 2+ signals and the duration of somatic Ca 2+ signals decreased when moving from ramified via hypertrophic to ameboid microglia. In contrast, the size of active compartments, the fraction and amplitude of somatic Ca 2+ signals and the duration of process Ca 2+ signals increased along this pathway.

Authors 12

1. Sofia Nevelchuk

   University of Tübingen

   Affiliation as printed

   Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Tübingen, Germany

2. Bianca Brawek

   University of Tübingen

   Affiliation as printed

   Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Tübingen, Germany

3. Niklas Schwarz

   Hertie Institute for Clinical Brain Research · University of Tübingen

   Affiliation as printed

   Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

4. Ariel A. Valiente‐Gabioud

   Max Planck Institute for Biological Intelligence

   Affiliation as printed

   Tools for Bio-Imaging, Max-Planck-Institute for Biological Intelligence, Martinsried, Germany

5. Thomas V. Wuttke

   Hertie Institute for Clinical Brain Research · University of Tübingen

   Affiliation as printed

   Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

   Department of Neurosurgery, University of Tübingen, Tübingen, Germany

6. Yury Kovalchuk

   University of Tübingen

   Affiliation as printed

   Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Tübingen, Germany

7. Henner Koch Aachen Department of Epileptology, Neurology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Epileptology, Neurology, RWTH Aachen University Hospital, Aachen, Germany

8. Anke Höllig Aachen Department of Neurosurgery

   RWTH Aachen University

   Affiliation as printed

   Department of Neurosurgery, RWTH Aachen University, Aachen, Germany

9. Frederik Steiner

   University of Tübingen

   Affiliation as printed

   Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Tübingen, Germany

10. Katherine Figarella

    University of Tübingen

    Affiliation as printed

    Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Tübingen, Germany

11. Oliver Griesbeck

    Max Planck Institute for Biological Intelligence

    Affiliation as printed

    Tools for Bio-Imaging, Max-Planck-Institute for Biological Intelligence, Martinsried, Germany

12. Olga Garaschuk corresponding

    University of Tübingen

    Affiliation as printed

    Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Tübingen, Germany