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Cell. 2014 Feb 13;156(4):825-35. doi: 10.1016/j.cell.2013.12.042.

Activity-driven local ATP synthesis is required for synaptic function.

Author information

1
Rockefeller/Sloan-Kettering/Weill Cornell Tri-Institutional Training Program in Chemical Biology, New York, NY 10065, USA; Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
2
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
3
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: taryan@med.cornell.edu.

Abstract

Cognitive function is tightly related to metabolic state, but the locus of this control is not well understood. Synapses are thought to present large ATP demands; however, it is unclear how fuel availability and electrical activity impact synaptic ATP levels and how ATP availability controls synaptic function. We developed a quantitative genetically encoded optical reporter of presynaptic ATP, Syn-ATP, and find that electrical activity imposes large metabolic demands that are met via activity-driven control of both glycolysis and mitochondrial function. We discovered that the primary source of activity-driven metabolic demand is the synaptic vesicle cycle. In metabolically intact synapses, activity-driven ATP synthesis is well matched to the energetic needs of synaptic function, which, at steady state, results in ∼10(6) free ATPs per nerve terminal. Despite this large reservoir of ATP, we find that several key aspects of presynaptic function are severely impaired following even brief interruptions in activity-stimulated ATP synthesis.

PMID:
24529383
PMCID:
PMC3955179
DOI:
10.1016/j.cell.2013.12.042
[Indexed for MEDLINE]
Free PMC Article
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