title: LTP- and LTD-inducing stimulations cause opposite changes in arc/arg3.1 mRNA level in hippocampal area CA1 in vivo.
abstract: Immediate early genes (IEGs) typically are the first genetic responders to a variety of cellular activations. The IEG that encodes activity-regulated cytoskeleton-associated protein (arc/arg3.1) has attracted much interest because its mRNA is transported to and translated near activated synapses. Moreover, arc has been implicated in both long-term potentiation (LTP) and long-term depression (LTD). However, little is known about the time course of altered arc expression during LTP and LTD. Here we characterized arc mRNA levels in area CA1 of the adult rat hippocampus in vivo after LTP- and LTD-inducing stimulations that were identical, except for the temporal patterning of the stimulation pulses. We observed a persistent increase in arc mRNA level during LTP. In contrast, during LTD, arc mRNA level first was decreased and then transiently increased relative to control level. These findings demonstrate that arc mRNA is regulated differently during LTP and LTD, and they provide evidence for stimulation-induced downregulation of mRNA availability during LTD. Findings of abbreviated LTD when transcription was inhibited indicate that the prolonged maintenance of the type of N-methyl-D-aspartate receptor-dependent LTD studied here requires de novo transcription. Furthermore, lack of evidence for a LTD-associated change in the mRNA level of the IEG zif268 demonstrates that the decrease in arc mRNA during LTD is not a general genetic response. Thus, the regulation of arc expression not only differs between LTP and LTD, but also diverges from that of other IEGs implicated in activity-dependent synaptic plasticity.
authors.affiliation: Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Eser
authors.initials: E
authors.lastname: Yilmaz-Rastoder
authors.forename: Takeaki
authors.initials: T
authors.lastname: Miyamae
authors.forename: Amy E
authors.initials: AE
authors.lastname: Braun
authors.forename: Edda
authors.initials: E
authors.lastname: Thiels
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics*; D036881:Long-Term Synaptic Depression / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein; D015763:2-Amino-5-phosphonovalerate
references.citation: J Comp Neurol. 1990 May 22;295(4):580-623
references.pmid: 2358523
references.citation: Learn Mem. 2003 Mar-Apr;10(2):99-107
references.pmid: 12663748
references.citation: Neuron. 2008 Jul 10;59(1):84-97
references.pmid: 18614031
references.citation: Neurobiol Learn Mem. 1998 Jul-Sep;70(1-2):37-43
references.pmid: 9753585
references.citation: Hippocampus. 2005;15(5):579-86
references.pmid: 15920719
references.citation: J Comp Neurol. 2006 Sep 20;498(3):317-29
references.pmid: 16871537
references.citation: Neuron. 2004 Sep 30;44(1):5-21
references.pmid: 15450156
references.citation: Eur J Neurosci. 2001 Mar;13(5):968-76
references.pmid: 11264669
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):316-21
references.pmid: 19116276
references.citation: J Neurosci. 2009 Jan 28;29(4):898-906
references.pmid: 19176799
references.citation: Rev Neurosci. 2001;12(2):121-40
references.pmid: 11392454
references.citation: J Neurosci. 2001 Aug 1;21(15):5484-93
references.pmid: 11466419
references.citation: Nature. 2004 Feb 19;427(6976):753-7
references.pmid: 14973490
references.citation: Nature. 2002 Aug 29;418(6901):970-5
references.pmid: 12198546
references.citation: Neuroscience. 1992;46(3):501-9
references.pmid: 1347648
references.citation: Nat Neurosci. 2001 Mar;4(3):289-96
references.pmid: 11224546
references.citation: J Neurochem. 2004 Jun;89(5):1111-8
references.pmid: 15147503
references.citation: Nat Neurosci. 1999 Dec;2(12):1120-4
references.pmid: 10570490
references.citation: J Neurosci. 2000 Nov 15;20(22):8572-6
references.pmid: 11069965
references.citation: Neuron. 1995 Feb;14(2):433-45
references.pmid: 7857651
references.citation: Science. 2006 Feb 17;311(5763):1008-12
references.pmid: 16484497
references.citation: J Neurosci. 2009 Feb 4;29(5):1525-37
references.pmid: 19193899
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7062-8
references.pmid: 11416188
references.citation: Nature. 1993 Jan 7;361(6407):31-9
references.pmid: 8421494
references.citation: J Neurosci. 2000 Oct 1;20(19):7199-207
references.pmid: 11007876
references.citation: Cell. 1992 Jul 10;70(1):105-13
references.pmid: 1352481
references.citation: Neuron. 2001 Apr;30(1):227-40
references.pmid: 11343657
references.citation: J Neurosci. 1998 Jan 1;18(1):26-35
references.pmid: 9412483
references.citation: J Neurosci. 2002 Mar 15;22(6):2054-62
references.pmid: 11896145
references.citation: Neuron. 2006 Nov 9;52(3):437-44
references.pmid: 17088210
references.citation: Behav Brain Res. 2003 Jun 16;142(1-2):17-30
references.pmid: 12798262
references.citation: Eur J Neurosci. 2006 Jul;24(2):555-63
references.pmid: 16903857
references.citation: J Neurosci. 1999 Jul 1;19(13):5683-92
references.pmid: 10377374
references.citation: Behav Genet. 1996 May;26(3):293-9
references.pmid: 8754252
references.citation: Bioessays. 2006 Aug;28(8):822-33
references.pmid: 16927307
references.citation: Exp Brain Res. 2010 Jan;200(2):125-40
references.pmid: 19690847
references.citation: Cell. 2001 Sep 7;106(5):607-17
references.pmid: 11551508
references.citation: Neural Plast. 2008;2008:269097
references.pmid: 19190776
references.citation: J Neurosci. 2008 Nov 12;28(46):11760-7
references.pmid: 19005037
references.citation: Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5734-8
references.pmid: 7777577
references.citation: Neurochem Res. 2010 Feb;35(2):239-46
references.pmid: 19731018
references.citation: Nature. 1994 Jun 9;369(6480):486-8
references.pmid: 7515479
references.citation: Science. 1994 Aug 19;265(5175):1104-7
references.pmid: 8066450
references.citation: Neuron. 2006 Nov 9;52(3):403-7
references.pmid: 17088207
references.citation: Cell. 2007 Jul 13;130(1):179-91
references.pmid: 17632064
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13342-7
references.pmid: 11087874
references.citation: Nat Rev Mol Cell Biol. 2004 Feb;5(2):89-99
references.pmid: 15040442
references.citation: Neuron. 2006 Nov 9;52(3):461-74
references.pmid: 17088212
references.citation: Neuron. 2008 Jul 10;59(1):70-83
references.pmid: 18614030
references.citation: J Neurophysiol. 1994 Dec;72(6):3009-16
references.pmid: 7897506
references.citation: Mol Cell Biol. 2005 Dec;25(23):10286-300
references.pmid: 16287845
references.citation: J Neurosci. 2007 Sep 26;27(39):10445-55
references.pmid: 17898216
references.citation: J Neurosci. 2005 Oct 12;25(41):9384-97
references.pmid: 16221847
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11771-5
references.pmid: 19556537
references.citation: J Neurosci Res. 2002 Apr 15;68(2):121-6
references.pmid: 11948657
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10718-23
references.pmid: 16020527
references.citation: Neuroscientist. 2003 Dec;9(6):463-74
references.pmid: 14678579
references.citation: J Neurosci. 2005 Feb 16;25(7):1761-8
references.pmid: 15716412
references.citation: Neurobiol Learn Mem. 2008 Mar;89(3):269-84
references.pmid: 17931913
references.citation: Neuron. 1998 Oct;21(4):741-51
references.pmid: 9808461
references.citation: Neuroscience. 1998 Oct;86(4):1023-9
references.pmid: 9697109
references.citation: J Neurosci. 2000 Jun 1;20(11):3993-4001
references.pmid: 10818134
references.citation: Neuron. 1998 Oct;21(4):869-83
references.pmid: 9808472
references.citation: BMJ. 1996 May 4;312(7039):1153
references.pmid: 8620137
references.citation: J Biol Chem. 2001 Jun 29;276(26):24044-50
references.pmid: 11306573