title: Motile axonal mitochondria contribute to the variability of presynaptic strength.
abstract: One of the most notable characteristics of synaptic transmission is the wide variation in synaptic strength in response to identical stimulation. In hippocampal neurons, approximately one-third of axonal mitochondria are highly motile, and some dynamically pass through presynaptic boutons. This raises a fundamental question: can motile mitochondria contribute to the pulse-to-pulse variability of presynaptic strength? Recently, we identified syntaphilin as an axonal mitochondrial-docking protein. Using hippocampal neurons and slices of syntaphilin knockout mice, we demonstrate that the motility of axonal mitochondria correlates with presynaptic variability. Enhancing mitochondrial motility increases the pulse-to-pulse variability, whereas immobilizing mitochondria reduces the variability. By dual-color live imaging at single-bouton levels, we further show that motile mitochondria passing through boutons dynamically influence synaptic vesicle release, mainly by altering ATP homeostasis in axons. Thus, our study provides insight into the fundamental properties of the CNS to ensure the plasticity and reliability of synaptic transmission.
authors.affiliation: Synaptic Functions Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, Maryland 20892-3706, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: Synaptic Functions Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, Maryland 20892-3706, USA.
authors.forename: Haifa
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Synaptic Functions Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, Maryland 20892-3706, USA.
authors.forename: Ping-Yue
authors.initials: PY
authors.lastname: Pan
authors.affiliation: Synaptic Functions Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, Maryland 20892-3706, USA.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Synaptic Functions Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, Maryland 20892-3706, USA.
authors.forename: Zu-Hang
authors.initials: ZH
authors.lastname: Sheng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D000255:Adenosine Triphosphate
references.citation: J Neurophysiol. 2002 Jul;88(1):98-106
references.pmid: 12091535
references.citation: Cell. 2008 Jan 11;132(1):137-48
references.pmid: 18191227
references.citation: J Mol Neurosci. 2013 Jan;49(1):223-30
references.pmid: 22772899
references.citation: Nat Rev Neurosci. 2006 Jul;7(7):563-74
references.pmid: 16791145
references.citation: J Neurosci. 2009 Jul 29;29(30):9429-38
references.pmid: 19641106
references.citation: Neuron. 1997 Apr;18(4):599-612
references.pmid: 9136769
references.citation: J Neurosci. 2010 Sep 1;30(35):11838-47
references.pmid: 20810903
references.citation: Neuron. 1999 Feb;22(2):395-409
references.pmid: 10069344
references.citation: Nat Cell Biol. 2000 Apr;2(4):197-204
references.pmid: 10783237
references.citation: Nat Rev Neurosci. 2012 Jan 05;13(2):77-93
references.pmid: 22218207
references.citation: Neuron. 2009 Aug 27;63(4):482-96
references.pmid: 19709630
references.citation: Neuron. 2005 Aug 4;47(3):365-78
references.pmid: 16055061
references.citation: J Neurosci. 2002 Dec 1;22(23):10267-76
references.pmid: 12451127
references.citation: Neuron. 1997 Mar;18(3):483-91
references.pmid: 9115741
references.citation: Nat Rev Neurosci. 2005 May;6(5):389-97
references.pmid: 15861181
references.citation: J Neurophysiol. 1998 Mar;79(3):1219-29
references.pmid: 9497403
references.citation: J Neurosci. 2006 Jun 28;26(26):7035-45
references.pmid: 16807333
references.citation: Nat Methods. 2009 Feb;6(2):161-6
references.pmid: 19122669
references.citation: Nat Rev Neurosci. 2009 May;10(5):373-83
references.pmid: 19377502
references.citation: Neuron. 2007 Sep 20;55(6):835-58
references.pmid: 17880890
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4885-90
references.pmid: 12682300
references.citation: Nat Rev Neurosci. 2002 Jul;3(7):497-516
references.pmid: 12094207
references.citation: Nature. 1993 Dec 9;366(6455):569-72
references.pmid: 7902955
references.citation: Nat Rev Neurosci. 2011 Jun 20;12(7):375-87
references.pmid: 21685931