Wnt Signaling Through Nitric Oxide Synthase Promotes the Formation of Multi-Innervated Spines.
LTP
Wnt signaling
multi-innervated spines
nitric oxide
structural plasticity
Journal
Frontiers in synaptic neuroscience
ISSN: 1663-3563
Titre abrégé: Front Synaptic Neurosci
Pays: Switzerland
ID NLM: 101548972
Informations de publication
Date de publication:
2020
2020
Historique:
received:
24
06
2020
accepted:
13
08
2020
entrez:
5
10
2020
pubmed:
6
10
2020
medline:
6
10
2020
Statut:
epublish
Résumé
Structural plasticity of synapses correlates with changes in synaptic strength. Dynamic modifications in dendritic spine number and size are crucial for long-term potentiation (LTP), the cellular correlate of learning and memory. Recent studies have suggested the generation of multi-innervated spines (MIS), in the form of several excitatory presynaptic inputs onto one spine, are crucial for hippocampal memory storage. However, little is known about the molecular mechanisms underlying MIS formation and their contribution to LTP. Using 3D enhanced resolution confocal images, we examined the contribution of Wnt synaptic modulators in MIS formation in the context of LTP. We show that blockage of endogenous Wnts with specific Wnt antagonists supresses the formation of MIS upon chemical LTP induction in cultured hippocampal neurons. Gain- and loss-of-function studies demonstrate that Wnt7a signaling promotes MIS formation through the postsynaptic Wnt scaffold protein Disheveled 1 (Dvl1) by stimulating neuronal nitric oxide (NO) synthase (nNOS). Subsequently, NO activates soluble guanylyl cyclase (sGC) to increase MIS formation. Consistently, we observed an enhanced frequency and amplitude of excitatory postsynaptic currents. Collectively, our findings identify a unique role for Wnt secreted proteins through nNOS/NO/sGC signaling to modulate MIS formation during LTP.
Identifiants
pubmed: 33013349
doi: 10.3389/fnsyn.2020.575863
pmc: PMC7509412
doi:
Types de publication
Journal Article
Langues
eng
Pagination
575863Subventions
Organisme : Medical Research Council
ID : MR/S012125/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 McLeod, Boyle, Marzo, Martin-Flores, Moe, Palomer, Gibb and Salinas.
Références
Cell. 2000 Mar 3;100(5):525-35
pubmed: 10721990
Neuron. 2004 Sep 30;44(1):5-21
pubmed: 15450156
Nat Neurosci. 2018 Aug;21(8):1137
pubmed: 29967466
Curr Biol. 2019 Nov 4;29(21):3600-3610.e4
pubmed: 31630953
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10732-7
pubmed: 21670302
J Biol Chem. 2006 Apr 28;281(17):11910-6
pubmed: 16501258
Neuron. 2009 May 28;62(4):510-25
pubmed: 19477153
Nat Commun. 2015 Sep 24;6:8302
pubmed: 26400647
Cell Signal. 2010 May;22(5):717-27
pubmed: 20006983
Nat Neurosci. 2014 Dec;17(12):1701-9
pubmed: 25383903
Curr Opin Neurobiol. 2018 Dec;53:90-95
pubmed: 29975877
Neurobiol Learn Mem. 2015 Oct;124:48-51
pubmed: 25933505
J Neurosci. 1998 Nov 1;18(21):8900-11
pubmed: 9786995
Cold Spring Harb Perspect Biol. 2011 Jun 01;3(6):
pubmed: 21555405
J Neurosci. 1988 Apr;8(4):1454-68
pubmed: 3282038
J Neurosci. 2010 Sep 1;30(35):11565-75
pubmed: 20810878
J Neurosci. 2011 Jun 29;31(26):9466-71
pubmed: 21715611
Cereb Cortex. 2014 Jul;24(7):1923-36
pubmed: 23448871
Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):E4142-51
pubmed: 24127602
Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4797-802
pubmed: 25825749
Hippocampus. 2011 Sep;21(9):990-8
pubmed: 20865734
Prog Brain Res. 1998;118:83-97
pubmed: 9932436
Neuron. 2020 Aug 5;107(3):522-537.e6
pubmed: 32464088
J Neurosci. 2002 Oct 15;22(20):8961-70
pubmed: 12388603
Mol Cell Neurosci. 2015 Sep;68:314-22
pubmed: 26311509
Mech Dev. 1999 May;83(1-2):27-37
pubmed: 10507837
J Neurosci. 2003 Jul 2;23(13):5503-6
pubmed: 12843250
J Neurosci. 1999 Nov 15;19(22):10153-63
pubmed: 10559423
Curr Biol. 2016 Oct 10;26(19):2551-2561
pubmed: 27593374
Nat Neurosci. 2018 May;21(5):671-682
pubmed: 29686261
Annu Rev Physiol. 2016;78:351-65
pubmed: 26863325
J Comp Neurol. 2005 Apr 4;484(2):183-90
pubmed: 15736233
Development. 2010 Jul;137(13):2215-25
pubmed: 20530549
PLoS One. 2013;8(2):e57292
pubmed: 23451200
Cell Rep. 2017 Oct 3;21(1):60-69
pubmed: 28978484
Nat Commun. 2019 Oct 23;10(1):4813
pubmed: 31645626
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18471-5
pubmed: 22025701
J Comp Neurol. 2001 Feb 26;431(1):1-10
pubmed: 11169986
J Neurosci. 2008 May 14;28(20):5178-88
pubmed: 18480274
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4176-81
pubmed: 17360496
Biochem Biophys Res Commun. 2014 Feb 7;444(2):189-94
pubmed: 24440698
J Cell Biol. 2008 Dec 15;183(6):1115-27
pubmed: 19075115
Cell Rep. 2018 Apr 24;23(4):1060-1071
pubmed: 29694885
J Biol Chem. 2008 Feb 29;283(9):5918-27
pubmed: 18096705
Neuron. 2006 Jun 15;50(6):897-909
pubmed: 16772171
J Neurosci. 2003 Sep 17;23(24):8498-505
pubmed: 13679418