The Arc of synaptic memory.
The immediate early gene Arc is emerging as a versatile, finely tuned system capable of coupling changes in neuronal activity patterns to synaptic plasticity, thereby optimizing information storage in the nervous system. Here, we attempt to overview the Arc system spanning from transcriptional regulation of the Arc gene, to dendritic transport, metabolism, and translation of Arc mRNA, to post-translational modification, localization, and degradation of Arc protein. Within this framework we discuss the function of Arc in regulation of actin cytoskeletal dynamics underlying consolidation of long-term potentiation (LTP) and regulation of AMPA-type glutamate receptor endocytosis underlying long-term depression (LTD) and homeostatic plasticity. Behaviorally, Arc has a key role in consolidation of explicit and implicit forms of memory, with recent work implicating Arc in adaptation to stress as well as maladaptive plasticity connected to drug addiction. Arc holds considerable promise as a "master regulator" of protein synthesis-dependent forms of synaptic plasticity, but the mechanisms that modulate and switch Arc function are only beginning to be elucidated.
Bramham
Clive R
CR
Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway. clive.bramham@biomed.uib.no
Alme
Maria N
MN
Bittins
Margarethe
M
Kuipers
Sjoukje D
SD
Nair
Rajeevkumar R
RR
Pai
Balagopal
B
Panja
Debabrata
D
Schubert
Manja
M
Soule
Jonathan
J
Tiron
Adrian
A
Wibrand
Karin
K
D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D008568:Memory / Q000502:physiology*; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein
Nat Rev Neurosci. 2007 Oct;8(10):776-89
17848965
J Comp Neurol. 2007 Jan 20;500(3):433-47
17120280
Nature. 2001 Mar 15;410(6826):372-6
11268214
Nat Neurosci. 2000 Mar;3(3):211-6
10700251
Neuroscience. 2003;121(4):975-82
14580947
Nature. 1988 Jul 14;334(6178):170-3
3386756
Mol Cell Biol. 2007 Mar;27(5):1974-89
17178834
Nature. 2004 May 13;429(6988):184-7
15107864
Genes Dev. 2007 Mar 15;21(6):708-18
17369403
Neuron. 2008 Nov 6;60(3):477-82
18995822
Eur J Neurosci. 2006 Jun;23(11):2829-46
16819972
Acta Pharmacol Sin. 2009 Mar;30(3):282-90
19262551
Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):316-21
19116276
J Neurosci. 2009 Jan 28;29(4):898-906
19176799
Nat Neurosci. 2008 Oct;11(10):1153-61
18758458
Eur J Neurosci. 2006 Mar;23(6):1501-11
16553613
Nature. 2008 Apr 10;452(7188):709-11
18401402
Cell. 2008 Oct 31;135(3):422-35
18984155
Eur J Neurosci. 2003 Nov;18(10):2707-12
14656319
J Neurosci. 2001 Aug 1;21(15):5484-93
11466419
Curr Opin Pharmacol. 2007 Feb;7(1):18-21
17049922
J Neurosci. 2005 Oct 19;25(42):9581-90
16237163
PLoS One. 2009;4(3):e4885
19290048
J Neurosci. 2006 May 31;26(22):5888-93
16738230
Eur J Neurosci. 2009 Feb;29(3):465-76
19222557
Learn Mem. 2007 Nov 14;14(11):758-70
18007019
Eur J Pharmacol. 2007 Jan 26;555(2-3):115-21
17112503
Curr Opin Neurobiol. 2005 Feb;15(1):121-8
15721754
J Nutr Health Aging. 2008 Jan;12(1):51S-7S
18165846
Neuron. 2003 May 8;38(3):447-60
12741991
J Biol Chem. 2008 Jan 4;283(1):582-592
17981809
Nat Neurosci. 1999 Dec;2(12):1120-4
10570490
Neuron. 1995 Feb;14(2):433-45
7857651
Neuroscience. 2004;125(1):7-11
15051140
Neuroscience. 1993 Sep;56(2):337-44
8247264
Brain Res. 2007 Jun 11;1153:20-33
17466953
Neuropharmacology. 2007 Jan;52(1):12-23
16949110
J Neurosci. 2003 Nov 26;23(34):10800-8
14645472
Nature. 2008 Oct 16;455(7215):894-902
18923511
J Neurosci. 2009 Feb 4;29(5):1525-37
19193899
Neuron. 2001 Apr;30(1):227-40
11343657
Nat Cell Biol. 2000 May;2(5):E85-90
10806494
J Neurosci. 1998 Jan 1;18(1):26-35
9412483
J Neurosci. 2004 Jul 21;24(29):6489-96
15269259
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2368-73
11842217
Neuron. 2009 Jan 15;61(1):10-26
19146809
J Neurosci. 2002 Mar 1;22(5):1532-40
11880483
Hippocampus. 2007;17(3):227-34
17286278
Curr Biol. 2006 Dec 5;16(23):2345-51
17141617
Annu Rev Neurosci. 2006;29:565-98
16776597
Neuron. 2006 Nov 9;52(3):437-44
17088210
Biochim Biophys Acta. 2008 Nov;1783(11):2145-54
18616965
Trends Biochem Sci. 2007 Sep;32(9):400-6
17693089
Neuroscience. 2007 Feb 9;144(3):969-84
17156936
J Neurosci. 2000 Sep 1;20(17):6385-93
10964944
Nature. 2005 Feb 3;433(7025):477-80
15690031
Nat Rev Mol Cell Biol. 2007 Dec;8(12):1006-16
17928811
Mol Biol Cell. 2008 May;19(5):2311-27
18305102
Neuropsychopharmacology. 2008 Jan;33(1):18-41
17728696
Cell. 2003 Feb 7;112(3):317-27
12581522
Nature. 2008 Feb 21;451(7181):1004-7
18235445
J Neurosci. 2002 Dec 1;22(23):10067-71
12451105
Hum Mol Genet. 2007 Dec 15;16(24):3047-58
17881655
Nature. 2004 Jun 17;429(6993):761-6
15190253
J Neurosci. 2006 Nov 22;26(47):12237-41
17122048
J Neurosci. 2007 Aug 22;27(34):9054-67
17715342
Neurosci Res. 2003 Dec;47(4):399-408
14630344
J Biol Chem. 2000 Jan 28;275(4):2647-53
10644725
Psychopharmacology (Berl). 2008 Dec;201(2):285-92
18704370
J Neurobiol. 1999 Feb 5;38(2):234-46
10022569
Curr Opin Neurobiol. 2008 Oct;18(5):524-31
18834940
Neuron. 2006 Nov 9;52(3):475-84
17088213
J Comp Neurol. 2003 Jun 9;460(4):563-72
12717714
Learn Mem. 2003 Mar-Apr;10(2):99-107
12663748
Prog Neurobiol. 2005 Jun;76(2):99-125
16099088
Neuron. 2002 Aug 1;35(3):535-45
12165474
Science. 2008 Mar 21;319(5870):1683-7
18309046
Eur Neuropsychopharmacol. 2008 Feb;18(2):107-16
17611082
Neural Plast. 2008;2008:269097
19190776
Eur J Neurosci. 2005 Jan;21(2):513-21
15673450
Biochem J. 2007 Apr 15;403(2):217-34
17376031
Eur J Neurosci. 2006 May;23(10):2814-8
16817885
J Neurosci. 2007 Dec 26;27(52):14349-57
18160642
Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5734-8
7777577
Cell. 2009 Feb 20;136(4):731-45
19239892
J Neurosci. 2008 Nov 12;28(46):11760-7
19005037
Neuroscience. 2008 Jun 26;154(3):1021-33
18501523
J Neurosci. 2000 May 15;20(10):RC76
10783400
Nat Neurosci. 2000 Jul;3(7):661-9
10862698
Nat Neurosci. 2007 Jun;10(6):727-34
17486101
J Neurosci. 2008 Mar 5;28(10):2589-600
18322102
J Neurosci. 2007 Mar 21;27(12):3252-9
17376985
Neuron. 2006 Nov 9;52(3):403-7
17088207
J Proteome Res. 2007 Mar;6(3):1059-71
17330943
Nat Genet. 1998 Nov;20(3):266-72
9806545
J Neurochem. 2006 Dec;99(5):1328-37
17064361
Nat Neurosci. 2007 Sep;10(9):1083-4
17726472
Curr Opin Cell Biol. 2004 Feb;16(1):80-5
15037309
Cell. 2007 Jul 13;130(1):179-91
17632064
Neuron. 2008 Jul 10;59(1):1-3
18614022
J Neurosci. 1988 Jan;8(1):176-84
3339407
Brain Res Mol Brain Res. 2004 Feb 5;121(1-2):131-6
14969744
Nat Neurosci. 2006 Jul;9(7):887-95
16732277
Neuron. 2007 May 24;54(4):559-66
17521569
Annu Rev Neurosci. 2008;31:47-67
18284372
Neuron. 2008 Jul 10;59(1):84-97
18614031
Science. 2006 Aug 25;313(5790):1141-4
16931766
Neuron. 2004 Aug 19;43(4):513-25
15312650
Proc Natl Acad Sci U S A. 2004 May 4;101(18):7181-6
15118105
Neurosci Lett. 2006 May 1;398(1-2):78-82
16412575
Biochemistry. 1986 Apr 22;25(8):2033-41
3707930
Eur J Neurosci. 2003 Jun;17(12):2679-89
12823475
Eur J Neurosci. 2005 May;21(9):2384-96
15932597
Neuroscience. 2007 Sep 21;148(4):925-36
17764852
J Neurosci. 2006 Feb 22;26(8):2167-73
16495443
J Neurosci. 2002 Sep 1;22(17):7453-61
12196567
Nat Rev Mol Cell Biol. 2004 Feb;5(2):89-99
15040442
Neuron. 2006 Nov 9;52(3):461-74
17088212
J Neurochem. 2007 Oct;103(2):626-36
17711418
Ann N Y Acad Sci. 2005 Jun;1048:259-71
16154938
Brain Res. 2002 Jan 11;924(2):133-40
11750898
Neuron. 2008 Jul 10;59(1):70-83
18614030
J Biol Chem. 1987 Dec 25;262(36):17299-303
3693353
Neuron. 2007 Aug 16;55(4):648-61
17698016
Neural Plast. 2007;2007:26496
18301726
Eur J Neurosci. 2005 Dec;22(12):2977-84
16367764
Eur J Neurosci. 2005 Nov;22(10):2560-8
16307598
J Neurosci. 2007 Sep 26;27(39):10445-55
17898216
Neurosci Lett. 2009 Aug 21;460(1):36-40
19446601
Hippocampus. 2006;16(3):216-24
16421862
Neuron. 2006 Nov 9;52(3):445-59
17088211
J Neurosci. 2005 Oct 12;25(41):9384-97
16221847
J Comp Neurol. 2001 Jul 9;435(4):406-17
11406822
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14403-8
14623964
Cell. 2008 Feb 22;132(4):645-60
18295581
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10718-23
16020527
J Neurosci. 2004 Nov 10;24(45):10191-200
15537891
Mol Cell Biol. 2006 Feb;26(4):1272-87
16449641
J Biol Chem. 2007 Oct 12;282(41):29738-47
17693403
Nat Neurosci. 2007 Mar;10(3):355-62
17277773
J Biol Chem. 2006 Oct 6;281(40):30195-211
16873368
J Neurosci. 2008 Nov 19;28(47):12383-95
19020031
Neuron. 1998 Oct;21(4):741-51
9808461
J Neurosci. 2000 Jun 1;20(11):3993-4001
10818134
Dev Cell. 2008 Jun;14(6):926-39
18539120
Neuron. 2003 Oct 9;40(2):347-59
14556713
J Neurosci. 2006 Jan 4;26(1):3-11
16399667
PLoS Biol. 2008 Oct 7;6(10):e246
18842068
J Neurosci. 2003 Jul 23;23(16):6443-51
12878684
J Neurosci. 2004 Mar 17;24(11):2648-55
15028757
Neuroscience. 2003;116(3):743-52
12573716
Int J Neuropsychopharmacol. 2009 Apr;12(3):423-9
19025723
J Neurosci. 1982 Mar;2(3):284-91
7062109
Hippocampus. 2006;16(3):208-15
16411232
J Neurosci. 2005 Oct 19;25(42):9686-93
16237173