title: Miro1-dependent mitochondrial positioning drives the rescaling of presynaptic Ca2+ signals during homeostatic plasticity.
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.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Vaccaro
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Devine
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: Nathalie F
authors.initials: NF
authors.lastname: Higgs
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK j.kittler@ucl.ac.uk.
authors.forename: Josef T
authors.identifier: 0000-0002-3437-9456
authors.initials: JT
authors.lastname: Kittler
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D015870:Gene Expression; D006706:Homeostasis; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; D020741:rho GTP-Binding Proteins; D002118:Calcium
keywords: Miro1; homeostatic; mitochondria; plasticity; synapse