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Miro1-dependent mitochondrial positioning drives the rescaling of presynaptic Ca2+ signals during homeostatic plasticity

Vaccaro, V; Devine, MJ; Higgs, NF; Kittler, JT; (2017) Miro1-dependent mitochondrial positioning drives the rescaling of presynaptic Ca2+ signals during homeostatic plasticity. EMBO Reports , 18 (2) pp. 231-240. 10.15252/embr.201642710. Green open access

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Abstract

Mitochondrial trafficking is influenced by neuronal activity, but it remains unclear how mitochondrial positioning influences neuronal transmission and plasticity. Here, we use live cell imaging with the genetically encoded presynaptically targeted Ca2+ indicator, SyGCaMP5, to address whether presynaptic Ca2+ responses are altered by mitochondria in synaptic terminals. We find that presynaptic Ca2+ signals, as well as neurotransmitter release, are significantly decreased in terminals containing mitochondria. Moreover, the localisation of mitochondria at presynaptic sites can be altered during long‐term activity changes, dependent on the Ca2+‐sensing function of the mitochondrial trafficking protein, Miro1. In addition, we find that Miro1‐mediated activity‐dependent synaptic repositioning of mitochondria allows neurons to homeostatically alter the strength of presynaptic Ca2+ signals in response to prolonged changes in neuronal activity. Our results support a model in which mitochondria are recruited to presynaptic terminals during periods of raised neuronal activity and are involved in rescaling synaptic signals during homeostatic plasticity.

Type: Article
Title: Miro1-dependent mitochondrial positioning drives the rescaling of presynaptic Ca2+ signals during homeostatic plasticity
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embr.201642710
Publisher version: http://doi.org/10.15252/embr.201642710
Language: English
Additional information: © 2016 The Authors. Published under the terms of the CC BY 4.0 license
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, homeostatic, Miro1, mitochondria, plasticity, synapse, AXON INITIAL SEGMENT, HIPPOCAMPAL SYNAPSES, DENDRITIC COMPLEXITY, EXCITATORY SYNAPSES, RELEASE PROBABILITY, SYNAPTIC PLASTICITY, TRANSMITTER RELEASE, NEURONAL-ACTIVITY, NERVE-TERMINALS, CALCIUM INFLUX
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1536052
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