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Elife. 2017 Apr 17;6. pii: e24241. doi: 10.7554/eLife.24241.

Monitoring ATP dynamics in electrically active white matter tracts.

Author information

1
Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany.
2
Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland.
3
Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
4
Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, Germany.
5
Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
6
Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.

Abstract

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.

KEYWORDS:

ATP; axon; imaging; mouse; myelin; neuroscience

PMID:
28414271
PMCID:
PMC5415357
DOI:
10.7554/eLife.24241
[Indexed for MEDLINE]
Free PMC Article

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