Brain Activity Regulates Loose Coupling Between Mitochondrial and Cytosolic Ca 2+ Transients

Nat Commun. 2019 Nov 21;10(1):5277. doi: 10.1038/s41467-019-13142-0.


Mitochondrial calcium ([Ca2+]mito) dynamics plays vital roles in regulating fundamental cellular and organellar functions including bioenergetics. However, neuronal [Ca2+]mito dynamics in vivo and its regulation by brain activity are largely unknown. By performing two-photon Ca2+ imaging in the primary motor (M1) and visual cortexes (V1) of awake behaving mice, we find that discrete [Ca2+]mito transients occur synchronously over somatic and dendritic mitochondrial network, and couple with cytosolic calcium ([Ca2+]cyto) transients in a probabilistic, rather than deterministic manner. The amplitude, duration, and frequency of [Ca2+]cyto transients constitute important determinants of the coupling, and the coupling fidelity is greatly increased during treadmill running (in M1 neurons) and visual stimulation (in V1 neurons). Moreover, Ca2+/calmodulin kinase II is mechanistically involved in modulating the dynamic coupling process. Thus, activity-dependent dynamic [Ca2+]mito-to-[Ca2+]cyto coupling affords an important mechanism whereby [Ca2+]mito decodes brain activity for the regulation of mitochondrial bioenergetics to meet fluctuating neuronal energy demands as well as for neuronal information processing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism*
  • Calcium / metabolism*
  • Calcium Signaling*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cytosol / metabolism*
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Microscopy, Fluorescence, Multiphoton
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Motor Cortex / cytology
  • Motor Cortex / metabolism
  • Neurons / metabolism*
  • Visual Cortex / cytology
  • Visual Cortex / metabolism*


  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium