title: Structural and molecular remodeling of dendritic spine substructures during long-term potentiation.
abstract: Synapses store information by long-lasting modifications of their structure and molecular composition, but the precise chronology of these changes has not been studied at single-synapse resolution in real time. Here we describe the spatiotemporal reorganization of postsynaptic substructures during long-term potentiation (LTP) at individual dendritic spines. Proteins translocated to the spine in four distinct patterns through three sequential phases. In the initial phase, the actin cytoskeleton was rapidly remodeled while active cofilin was massively transported to the spine. In the stabilization phase, cofilin formed a stable complex with F-actin, was persistently retained at the spine, and consolidated spine expansion. In contrast, the postsynaptic density (PSD) was independently remodeled, as PSD scaffolding proteins did not change their amount and localization until a late protein synthesis-dependent third phase. Our findings show how and when spine substructures are remodeled during LTP and explain why synaptic plasticity rules change over time.
authors.affiliation: RIKEN-MIT Neuroscience Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: mbosch@mit.edu.
authors.forename: Miquel
authors.initials: M
authors.lastname: Bosch
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Castro
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Saneyoshi
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Matsuno
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Mriganka
authors.initials: M
authors.lastname: Sur
authors.affiliation: RIKEN-MIT Neuroscience Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan; Saitama University Brain Science Institute, Saitama University, Saitama 338-8570, Japan. Electronic address: yhayashi@brain.riken.jp.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000648:ultrastructure*; D009924:Organ Culture Techniques; D057907:Post-Synaptic Density / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D014161:Transduction, Genetic
chemical_list: D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid
references.citation: Nature. 2009 Mar 19;458(7236):299-304
references.pmid: 19295602
references.citation: Nat Rev Neurosci. 2009 Dec;10(12):850-60
references.pmid: 19927149
references.citation: Cell. 2001 May 4;105(3):331-43
references.pmid: 11348590
references.citation: Cell. 2009 Apr 3;137(1):159-71
references.pmid: 19345194
references.citation: Neuroscience. 1995 Aug;67(4):799-807
references.pmid: 7675206
references.citation: J Neurosci. 2006 Jul 19;26(29):7693-706
references.pmid: 16855097
references.citation: Nat Neurosci. 2004 Oct;7(10):1104-12
references.pmid: 15361876
references.citation: FASEB J. 2008 May;22(5):1581-96
references.pmid: 18184720
references.citation: Rev Neurosci. 2001;12(1):51-68
references.pmid: 11236065
references.citation: J Neurosci. 2001 Feb 15;21(4):1211-7
references.pmid: 11160391
references.citation: Neuron. 2004 Sep 30;44(1):5-21
references.pmid: 15450156
references.citation: J Biol Chem. 2007 May 4;282(18):13692-702
references.pmid: 17360713
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6418-23
references.pmid: 17404223
references.citation: J Neurosci. 2008 May 28;28(22):5740-51
references.pmid: 18509035
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):E442-51
references.pmid: 22308427
references.citation: J Neurosci. 1989 Aug;9(8):2982-97
references.pmid: 2769375
references.citation: Science. 2000 Mar 24;287(5461):2262-7
references.pmid: 10731148
references.citation: Neuropharmacology. 2013 Jan;64:27-36
references.pmid: 22820276
references.citation: J Neurosci. 2009 Sep 30;29(39):12167-73
references.pmid: 19793974
references.citation: Neuron. 2009 Nov 12;64(3):381-90
references.pmid: 19914186
references.citation: Trends Neurosci. 2004 Aug;27(8):445-6
references.pmid: 15271490
references.citation: Nat Rev Neurosci. 2011 Jan;12(1):17-30
references.pmid: 21170072
references.citation: Physiology (Bethesda). 2009 Dec;24:357-66
references.pmid: 19996366
references.citation: Science. 2005 Nov 4;310(5749):866-9
references.pmid: 16272125
references.citation: Neuron. 2004 Oct 28;44(3):453-67
references.pmid: 15504326
references.citation: J Neurosci. 2004 Oct 20;24(42):9324-31
references.pmid: 15496668
references.citation: EMBO J. 2010 Jun 2;29(11):1889-902
references.pmid: 20407421
references.citation: Neuron. 2008 Dec 10;60(5):788-802
references.pmid: 19081375
references.citation: Neuron. 2008 Mar 13;57(5):719-29
references.pmid: 18341992
references.citation: Mol Cell Neurosci. 2006 Apr;31(4):702-12
references.pmid: 16504537
references.citation: Curr Biol. 2002 Jan 8;12(1):79-84
references.pmid: 11790308
references.citation: Nature. 2004 Jun 17;429(6993):761-6
references.pmid: 15190253
references.citation: Curr Opin Neurobiol. 2012 Jun;22(3):383-8
references.pmid: 21963169
references.citation: Cell Mol Life Sci. 2008 Sep;65(17):2688-701
references.pmid: 18488141
references.citation: Science. 2008 Mar 21;319(5870):1683-7
references.pmid: 18309046
references.citation: Nat Neurosci. 2006 Feb;9(2):234-42
references.pmid: 16415866
references.citation: Nat Rev Neurosci. 2008 May;9(5):344-56
references.pmid: 18425089
references.citation: J Cell Biol. 2009 Jul 13;186(1):85-97
references.pmid: 19596849
references.citation: Nature. 2011 Apr 7;472(7341):100-4
references.pmid: 21423166
references.citation: Annu Rev Biochem. 2007;76:823-47
references.pmid: 17243894
references.citation: J Cell Biol. 2001 Apr 2;153(1):75-86
references.pmid: 11285275
references.citation: J Neurosci. 2007 May 16;27(20):5363-72
references.pmid: 17507558
references.citation: J Cell Biochem. 2009 Dec 15;108(6):1252-62
references.pmid: 19862699
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12039-44
references.pmid: 18697934
references.citation: Nat Neurosci. 2010 Oct;13(10):1208-15
references.pmid: 20835250
references.citation: Neuron. 2004 Sep 30;44(1):59-73
references.pmid: 15450160
references.citation: Neuron. 2010 Jul 15;67(1):86-99
references.pmid: 20624594
references.citation: Neuron. 2004 Dec 2;44(5):749-57
references.pmid: 15572107
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15951-6
references.pmid: 20733080
references.citation: J Neurosci. 2005 Jan 26;25(4):799-807
references.pmid: 15673659
references.citation: Biochemistry. 2003 Nov 25;42(46):13363-70
references.pmid: 14621980
references.citation: Mol Cell. 2006 Oct 6;24(1):13-23
references.pmid: 17018289
references.citation: Nat Neurosci. 2000 Sep;3(9):881-6
references.pmid: 10966618
references.citation: J Cell Sci. 2006 Jul 15;119(Pt 14):2871-81
references.pmid: 16803871
references.citation: Neuron. 2011 Jan 13;69(1):132-46
references.pmid: 21220104
references.citation: J Neurosci. 2010 Sep 1;30(35):11565-75
references.pmid: 20810878
references.citation: Nature. 2007 Dec 20;450(7173):1195-200
references.pmid: 18097401