Frequency-and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical neurons

Ohad Stoler, Alexandra Stavsky, Yana Khrapunsky, Israel Melamed, Grace Stutzmann, Daniel Gitler, Israel Sekler, Ilya Fleidervish

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondrial activity is crucial for the plasticity of central synapses, but how the firing pattern of pre-and postsynaptic neurons affects the mitochondria remains elusive. We recorded changes in the fluorescence of cytosolic and mitochondrial Ca2+ indicators in cell bodies, axons, and dendrites of cortical pyramidal neurons in mouse brain slices while evoking pre-and postsynaptic spikes. Postsynaptic spike firing elicited fast mitochondrial Ca2+ responses that were about threefold larger in the somas and apical dendrites than in basal dendrites and axons. The amplitude of these responses and metabolic activity were extremely sensitive to the firing frequency. Furthermore, while an EPSP alone caused no detectable Ca2+ elevation in the dendritic mitochondria, the coincidence of EPSP with a backpropagating spike produced prominent, highly localized mitochondrial Ca2+ hotspots. Our results indicate that mitochondria decode the spike firing frequency and the Hebbian temporal coincidences into the Ca2+ signals, which are further translated into the metabolic output and most probably lead to long-term changes in synaptic efficacy.

Original languageEnglish
Article numbere74606
JournaleLife
Volume11
DOIs
StatePublished - 1 Feb 2022

Keywords

  • Action potential
  • Axon
  • Ca signaling
  • Cortical pyramidal neuron
  • Dendrite
  • Mitochondria
  • NAD(P)H oxidation
  • Spike-timing-dependent plasticity

ASJC Scopus subject areas

  • Neuroscience (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)

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