title: Dynamic microtubules promote synaptic NMDA receptor-dependent spine enlargement.
abstract: Most excitatory synaptic terminals in the brain impinge on dendritic spines. We and others have recently shown that dynamic microtubules (MTs) enter spines from the dendritic shaft. However, a direct role for MTs in long-lasting spine plasticity has yet to be demonstrated and it remains unclear whether MT-spine invasions are directly influenced by synaptic activity. Lasting changes in spine morphology and synaptic strength can be triggered by activation of synaptic NMDA receptors (NMDARs) and are associated with learning and memory processes. To determine whether MTs are involved in NMDAR-dependent spine plasticity, we imaged MT dynamics and spine morphology in live mouse hippocampal pyramidal neurons before and after acute activation of synaptic NMDARs. Synaptic NMDAR activation promoted MT-spine invasions and lasting increases in spine size, with invaded spines exhibiting significantly faster and more growth than non-invaded spines. Even individual MT invasions triggered rapid increases in spine size that persisted longer following NMDAR activation. Inhibition of either NMDARs or dynamic MTs blocked NMDAR-dependent spine growth. Together these results demonstrate for the first time that MT-spine invasions are positively regulated by signaling through synaptic NMDARs, and contribute to long-lasting structural changes in targeted spines.
authors.affiliation: Neuroscience Training Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Elliott B
authors.initials: EB
authors.lastname: Merriam
authors.forename: Derek C
authors.initials: DC
authors.lastname: Lumbard
authors.forename: Chris
authors.initials: C
authors.lastname: Viesselmann
authors.forename: Jason
authors.initials: J
authors.lastname: Ballweg
authors.forename: Matthew
authors.initials: M
authors.lastname: Stevenson
authors.forename: Lauren
authors.initials: L
authors.lastname: Pietila
authors.forename: Xindao
authors.initials: X
authors.lastname: Hu
authors.forename: Erik W
authors.initials: EW
authors.lastname: Dent
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
references.citation: Nat Cell Biol. 2011 Jan;13(1):40-8
references.pmid: 21151132
references.citation: Neuron. 2009 Jan 15;61(1):85-100
references.pmid: 19146815
references.citation: Neuron. 2008 Mar 13;57(5):719-29
references.pmid: 18341992
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3549-54
references.pmid: 19208802
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15951-6
references.pmid: 20733080
references.citation: J Vis Exp. 2011 Jan 24;(47):
references.pmid: 21304471
references.citation: Neuron. 2005 Jul 7;47(1):85-100
references.pmid: 15996550
references.citation: Nature. 2002 Dec 19-26;420(6917):788-94
references.pmid: 12490942
references.citation: J Neurosci. 2008 Nov 12;28(46):12120-4
references.pmid: 19005076
references.citation: J Neurosci. 2008 Dec 3;28(49):13094-105
references.pmid: 19052200
references.citation: Neuron. 2001 Jan;29(1):243-54
references.pmid: 11182095
references.citation: Nat Rev Neurosci. 2008 Nov;9(11):813-25
references.pmid: 18854855
references.citation: Neuron. 2007 Nov 21;56(4):640-56
references.pmid: 18031682
references.citation: Methods. 2001 May;24(1):35-42
references.pmid: 11327800
references.citation: Nat Protoc. 2006;1(5):2406-15
references.pmid: 17406484
references.citation: Neuron. 1998 Nov;21(5):1151-62
references.pmid: 9856470
references.citation: Neuron. 1998 Nov;21(5):1163-75
references.pmid: 9856471
references.citation: Nature. 2002 Dec 19-26;420(6917):812-6
references.pmid: 12490949
references.citation: Nat Cell Biol. 2003 Jul;5(7):599-609
references.pmid: 12833063
references.citation: Trends Cell Biol. 2008 May;18(5):210-9
references.pmid: 18394899
references.citation: Curr Opin Neurobiol. 2011 Feb;21(1):175-81
references.pmid: 20832290
references.citation: Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):829-42
references.pmid: 12740130
references.citation: Curr Opin Neurobiol. 2008 Oct;18(5):524-31
references.pmid: 18834940
references.citation: Nature. 2009 Dec 17;462(7275):915-9
references.pmid: 19946267
references.citation: J Neurosci. 2006 Aug 2;26(31):8137-47
references.pmid: 16885227
references.citation: Neurosci Res. 2007 Jan;57(1):1-9
references.pmid: 17070951
references.citation: Nat Cell Biol. 2008 Jan;10(1):19-29
references.pmid: 18066053
references.citation: Neuron. 2010 Jul 15;67(1):86-99
references.pmid: 20624594
references.citation: J Neurosci. 2011 Jun 1;31(22):8194-209
references.pmid: 21632941
references.citation: Nat Neurosci. 2004 Oct;7(10):1104-12
references.pmid: 15361876
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14437-42
references.pmid: 20660727
references.citation: Nature. 2009 Dec 17;462(7275):920-4
references.pmid: 19946265
references.citation: J Neurosci. 2010 Sep 22;30(38):12733-44
references.pmid: 20861378
references.citation: Nature. 2009 Jan 15;457(7227):313-7
references.pmid: 19005470
references.citation: J Neurosci. 2010 Sep 1;30(35):11565-75
references.pmid: 20810878