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@ARTICLE{Mller:162711,
      author       = {Müller, Franziska E and Cherkas, Volodymyr and Stopper,
                      Gebhard and Caudal, Laura C and Stopper, Laura and
                      Kirchhoff, Frank and Henneberger, Christian and Ponimaskin,
                      Evgeni G and Zeug, Andre},
      title        = {{E}lucidating regulators of astrocytic {C}a2+ signaling via
                      multi-threshold event detection ({MTED}).},
      journal      = {Glia},
      volume       = {69},
      number       = {12},
      issn         = {1098-1136},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley-Liss},
      reportid     = {DZNE-2021-01368},
      pages        = {2798 - 2811},
      year         = {2021},
      note         = {(CC BY-NC)},
      abstract     = {Recent achievements in indicator optimization and imaging
                      techniques promote the advancement of functional imaging to
                      decipher complex signaling processes in living cells, such
                      as Ca2+ activity patterns. Astrocytes are important
                      regulators of the brain network and well known for their
                      highly complex morphology and spontaneous Ca2+ activity.
                      However, the astrocyte community is lacking standardized
                      methods to analyze and interpret Ca2+ activity recordings,
                      hindering global comparisons. Here, we present a
                      biophysically-based analytical concept for deciphering the
                      complex spatio-temporal changes of Ca2+ biosensor
                      fluorescence for understanding the underlying signaling
                      mechanisms. We developed a pixel-based multi-threshold event
                      detection (MTED) analysis of multidimensional data, which
                      accounts for signal strength as an additional signaling
                      dimension and provides the experimenter with a comprehensive
                      toolbox for a differentiated and in-depth characterization
                      of fluorescence signals. MTED was validated by analyzing
                      astrocytic Ca2+ activity across Ca2+ indicators, imaging
                      setups, and model systems from primary cell culture to
                      awake, head-fixed mice. We identified extended Ca2+ activity
                      at 25°C compared to 37°C physiological body temperature
                      and dissected how neuronal activity shapes long-lasting
                      astrocytic Ca2+ activity. Our MTED strategy, as a
                      parameter-free approach, is easily transferrable to other
                      fluorescent indicators and biosensors and embraces the
                      additional dimensionality of signaling activity strength. It
                      will also advance the definition of standardized procedures
                      and parameters to improve comparability of research data and
                      reports.},
      keywords     = {Animals / Astrocytes: metabolism / Brain: diagnostic
                      imaging / Brain: metabolism / Calcium: metabolism / Calcium
                      Signaling: physiology / Mice / Neurons: metabolism / Ca2+
                      (Other) / GCaMP (Other) / MTED (Other) / astrocyte (Other) /
                      biosensor (Other)},
      cin          = {AG Henneberger},
      ddc          = {610},
      cid          = {I:(DE-2719)1013029},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34388285},
      doi          = {10.1002/glia.24070},
      url          = {https://pub.dzne.de/record/162711},
}