Activity-driven local ATP synthesis is required for synaptic function
By Vidhya Rangaraju, Nathaniel T Calloway, T. A. Ryan. Cell, 2014
748 citations recorded by the source corpus.
Summary 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 ~ 106 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.
Subfields: Cellular and Molecular Neuroscience, Materials Chemistry, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/5860cd1f22f2d6355c7e7ae55db67c864a6ceaf6
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In Cellular and Molecular Neuroscience
In Molecular Biology
Citations in the corpus
- A cellular perspective on brain energy metabolism and functional imaging. (2015, background): “Recent evidence confirms this view by identifying, in addition to postsynaptic potentials, presynaptic vesicle recycling as an additional energy-consuming process (Rangaraju et al., 2014).”
- Brain metabolism in health, aging, and neurodegeneration (2017, neutral): “…consumption as large amounts of ATP are required to support the activities of neurotransmitter transporters, and membrane Na+ and Ca2+ pumps that rapidly restore gradients of these ions after synapse activation (Attwell & Laughlin, 2001; Alle et al, 2009; Harris et al, 2012; Rangaraju et al, 2014).”