Brain activity regulates loose coupling between mitochondrial and cytosolic Ca2+ transients

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. Mitochondrial calcium signaling plays an important role in neuronal bioenergetics yet its regulation by brain activity in vivo is not understood. Here, the authors show that mitochondrial and cytosolic calcium transients are dynamically coupled as a function of brain activity.

• Publication year

  2019

• Venue

  Nature Communications

• Publication date

  2019-10-24

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41467-019-13142-0PMID 31754099PMCID 6872662
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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