Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical
- Ben Gurion University of the Negev, Israel
- Rosalind Franklin University of Medicine and Science, United States
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.
Data availability
A representative subset of the raw electrical recording and imaging data has been deposited to Dryad (https://doi.org/10.5061/dryad.sxksn0348). The dataset contains the Microcal Origin opj files of the electrical and optical recordings and quantitative analysis of the data. We are unable to make all raw electrical recording and imaging data publicly available as due to the large size of our raw dataset (>10TB). Interested researchers should contact the corresponding author to gain access to the raw data.
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Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical neuronsDryad Digital Repository, doi:10.5061/dryad.sxksn0348.
Article and author information
Author details
Funding
Israel Science Foundation (1384/19)
- Ilya Fleidervish
Israel Science Foundation (1310/19)
- Daniel Gitler
National Institutes of Health (RF1 AG065628)
- Israel Sekler
National Institutes of Health (RF1 AG065628)
- Grace E Stutzmann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were approved by the Animal Care and Use Committee of Ben Gurion University of the Negev (protocol #IL-68-09-2019).
Copyright
© 2022, Stoler et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical
eLife 11:e74606.
https://doi.org/10.7554/eLife.74606
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