Monitoring ATP dynamics in electrically active white matter tracts
Andrea Trevisiol,
Aiman S Saab,
Ulrike Winkler,
Grit Marx,
Hiromi Imamura,
Wiebke Möbius,
Kathrin Kusch,
Klaus-Armin Nave,
Johannes Hirrlinger
Affiliations
Andrea Trevisiol
Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
Aiman S Saab
Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany; Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland
Ulrike Winkler
Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, Germany
Grit Marx
Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, Germany
Hiromi Imamura
Graduate School of Biostudies, Kyoto University, Kyoto, Japan
Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany
Kathrin Kusch
Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany; Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, Germany
In several neurodegenerative diseases and myelin disorders, the degeneration profiles of myelinated axons are compatible with underlying energy deficits. However, it is presently impossible to measure selectively axonal ATP levels in the electrically active nervous system. We combined transgenic expression of an ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological recordings of acutely isolated optic nerves. This allowed us to monitor dynamic changes and activity-dependent axonal ATP homeostasis at the cellular level and in real time. We find that changes in ATP levels correlate well with compound action potentials. However, this correlation is disrupted when metabolism of lactate is inhibited, suggesting that axonal glycolysis products are not sufficient to maintain mitochondrial energy metabolism of electrically active axons. The combined monitoring of cellular ATP and electrical activity is a novel tool to study neuronal and glial energy metabolism in normal physiology and in models of neurodegenerative disorders.
