title: Molecular mechanisms of homeostatic synaptic downscaling.
abstract: Homeostatic synaptic downscaling is a negative feedback response to chronic elevated network activity to reduce the firing rate of neurons. This form of synaptic plasticity decreases the strength of individual synapses to the same proportion, or in a multiplicative manner. Because of this, synaptic downscaling has been hypothesized to counter the potential run-away excitation due to Hebbian type of long term potentiation (LTP), while preserving relative synaptic weight encoded in individual synapses and thus memory information. In this article, we will review the current knowledge on the signaling and molecular mechanisms of synaptic downscaling. Specifically, we focus on three general areas. First the functional roles of several immediate early genes such as Plk2, Homer1a, Arc and Narp are discussed. Secondly, we examine the current knowledge on the regulation of synaptic protein levels by ubiquitination and transcriptional repression in synaptic downscaling. Thirdly, we review the dynamics of signaling molecules such as kinases and phosphatases critical for synaptic downscaling, and their regulation of synaptic scaffolding proteins. Finally we briefly discuss the heterogeneity of homeostatic synaptic downscaling mechanisms. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.
authors.affiliation: Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Siddoway
authors.affiliation: Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
authors.forename: Hailong
authors.initials: H
authors.lastname: Hou
authors.affiliation: Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. Electronic address: hugh_xia@yahoo.com.
authors.forename: Houhui
authors.initials: H
authors.lastname: Xia
mesh_terms: D000818:Animals; D017781:Genes, Immediate-Early / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D009473:Neuronal Plasticity; D013569:Synapses / Q000378:metabolism*; D054875:Ubiquitination
keywords: Immediate early genes; Phosphorylation; Proteasome degradation; Synapse; Synaptic depression; Synaptic scaling
references.citation: J Neurosci. 2012 Sep 12;32(37):12841-7
references.pmid: 22973007
references.citation: Nat Neurosci. 2010 Sep;13(9):1090-7
references.pmid: 20729843
references.citation: Neuron. 2010 Dec 22;68(6):1128-42
references.pmid: 21172614
references.citation: Neuron. 2011 Mar 10;69(5):957-73
references.pmid: 21382555
references.citation: J Neurosci. 2001 Oct 1;21(19):RC170
references.pmid: 11567081
references.citation: J Neurosci. 2003 Nov 26;23(34):10841-51
references.pmid: 14645477
references.citation: Neuron. 1998 Nov;21(5):1067-78
references.pmid: 9856462
references.citation: EMBO J. 1999 Oct 15;18(20):5528-39
references.pmid: 10523297
references.citation: J Neurochem. 2006 Sep;98(6):1841-51
references.pmid: 16899074
references.citation: J Neurosci. 2011 May 4;31(18):6800-8
references.pmid: 21543610
references.citation: J Neurochem. 2011 Oct;119(1):27-39
references.pmid: 21338354
references.citation: Nature. 2006 Jun 29;441(7097):1144-8
references.pmid: 16810255
references.citation: Cell. 2012 May 11;149(4):886-98
references.pmid: 22579289
references.citation: Nat Neurosci. 2010 Oct;13(10):1199-207
references.pmid: 20802490
references.citation: Neuron. 1999 Jun;23(2):309-23
references.pmid: 10399937
references.citation: J Neurosci. 2010 Dec 8;30(49):16718-29
references.pmid: 21148011
references.citation: J Neurosci. 2011 Feb 23;31(8):3077-81
references.pmid: 21414928
references.citation: J Neurosci. 2010 May 26;30(21):7168-78
references.pmid: 20505084
references.citation: J Neurosci. 2013 Jul 3;33(27):11206-11
references.pmid: 23825423
references.citation: Science. 2003 Nov 21;302(5649):1368-73
references.pmid: 14576440
references.citation: Neuron. 2006 Nov 9;52(3):475-84
references.pmid: 17088213
references.citation: Neuron. 2010 Nov 4;68(3):512-28
references.pmid: 21040851
references.citation: J Neurosci. 2012 Jan 18;32(3):989-94
references.pmid: 22262897
references.citation: Neuron. 2011 Dec 8;72(5):806-18
references.pmid: 22153376
references.citation: EMBO J. 2004 Mar 10;23(5):1040-50
references.pmid: 14976558
references.citation: Nature. 1998 Feb 26;391(6670):892-6
references.pmid: 9495341
references.citation: Mol Cell Biol. 2008 Apr;28(8):2559-66
references.pmid: 18250156
references.citation: J Neurosci. 2008 Jun 25;28(26):6583-91
references.pmid: 18579731
references.citation: Science. 1993 Aug 20;261(5124):1051-5
references.pmid: 8394601
references.citation: Neuron. 2007 Nov 8;56(3):488-502
references.pmid: 17988632
references.citation: Neuron. 2013 Jan 9;77(1):99-114
references.pmid: 23312519
references.citation: Nat Neurosci. 2011 Feb;14(2):126-8
references.pmid: 21270777
references.citation: Neuroscience. 2010 Dec 29;171(4):1016-31
references.pmid: 20888892
references.citation: Neuron. 2009 Jan 15;61(1):71-84
references.pmid: 19146814
references.citation: J Neurosci. 1996 Apr 15;16(8):2463-78
references.pmid: 8786423
references.citation: Neuron. 2008 May 22;58(4):571-83
references.pmid: 18498738
references.citation: Cell. 1996 Dec 27;87(7):1203-14
references.pmid: 8980227
references.citation: J Neurosci. 2004 Jul 7;24(27):6152-60
references.pmid: 15240807
references.citation: Nat Neurosci. 2012 Dec;15(12):1655-66
references.pmid: 23143515
references.citation: J Neurosci. 2012 Apr 11;32(15):5126-31
references.pmid: 22496558
references.citation: Neuron. 2001 Dec 20;32(6):1133-48
references.pmid: 11754843
references.citation: J Neurosci. 2012 Sep 26;32(39):13529-36
references.pmid: 23015442
references.citation: Nat Neurosci. 2011 Feb;14(2):181-9
references.pmid: 21186356
references.citation: Neuron. 2006 Nov 9;52(3):445-59
references.pmid: 17088211
references.citation: J Biol Chem. 2012 Sep 7;287(37):30967-74
references.pmid: 22822052
references.citation: Nat Neurosci. 2003 Mar;6(3):231-42
references.pmid: 12577062
references.citation: Neurochem Int. 2006 May-Jun;48(6-7):643-9
references.pmid: 16546297