Activity-driven local ATP synthesis is required for synaptic function.
Cell
; 156(4): 825-35, 2014 Feb 13.
Article
en En
| MEDLINE
| ID: mdl-24529383
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 â¼10(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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sinapsis
/
Adenosina Trifosfato
/
Mitocondrias
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos