title: Bridging the interval: theory and neurobiology of trace conditioning.
abstract: An early finding in the behavioral analysis of learning was that conditioned responding weakens as the conditioned stimulus (CS) and unconditioned stimulus (US) are separated in time. This "trace" conditioning effect has been the focus of years of research in associative learning. Theoretical accounts of trace conditioning have focused on mechanisms that allow associative learning to occur across long intervals between the CS and US. These accounts have emphasized degraded contingency effects, timing mechanisms, and inhibitory learning. More recently, study of the neurobiology of trace conditioning has shown that even a short interval between the CS and US alters the circuitry recruited for learning. Here, we review some of the theoretical and neurobiological mechanisms underlying trace conditioning with an emphasis on recent studies of trace fear conditioning. Findings across many studies have implications not just for how we think about time and conditioning, but also for how we conceptualize fear conditioning in general, suggesting that circuitry beyond the usual suspects needs to be incorporated into current thinking about fear, learning, and anxiety.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, United States. Electronic address: raybuck@ohsu.edu.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Raybuck
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, United States. Electronic address: lattalm@ohsu.edu.
authors.forename: K Matthew
authors.initials: KM
authors.lastname: Lattal
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D003214:Conditioning, Classical; D005239:Fear / Q000502:physiology*; D011582:Psychological Theory
keywords: Amygdala; Consolidation; Fear; Hippocampus; Learning theory; Memory; Neurobiology
references.citation: Eur J Neurosci. 2006 Jan;23(1):251-60
references.pmid: 16420434
references.citation: Front Behav Neurosci. 2011 Dec 27;5:89
references.pmid: 22207842
references.citation: J Comp Physiol Psychol. 1973 May;83(2):198-207
references.pmid: 4706590
references.citation: J Neurosci. 2004 Jan 7;24(1):218-28
references.pmid: 14715954
references.citation: Neurobiol Learn Mem. 2009 Jan;91(1):73-80
references.pmid: 18952186
references.citation: Neurobiol Learn Mem. 2004 May;81(3):172-84
references.pmid: 15082019
references.citation: Cortex. 2013 May;49(5):1195-205
references.pmid: 22789779
references.citation: Psychopharmacology (Berl). 2007 Feb;190(3):343-52
references.pmid: 17136517
references.citation: Neurobiol Learn Mem. 2010 Oct;94(3):353-63
references.pmid: 20727979
references.citation: J Neurosci. 2006 Aug 23;26(34):8702-6
references.pmid: 16928858
references.citation: Curr Biol. 2013 Mar 18;23(6):467-72
references.pmid: 23453952
references.citation: J Exp Psychol Anim Behav Process. 2001 Oct;27(4):394-406
references.pmid: 11676088
references.citation: Behav Neurosci. 2009 Oct;123(5):1095-101
references.pmid: 19824776
references.citation: Behav Neurosci. 2006 Apr;120(2):482-7
references.pmid: 16719711
references.citation: Behav Neurosci. 1992 Apr;106(2):274-85
references.pmid: 1590953
references.citation: Learn Mem. 2008 Apr 25;15(5):368-72
references.pmid: 18441294
references.citation: Learn Mem. 2013 Feb 19;20(3):156-63
references.pmid: 23422280
references.citation: Neurobiol Learn Mem. 2007 May;87(4):464-75
references.pmid: 17251041
references.citation: Neuron. 2010 Jan 14;65(1):7-19
references.pmid: 20152109
references.citation: J Neurosci. 2008 Apr 9;28(15):4028-36
references.pmid: 18400902
references.citation: Hippocampus. 2002;12(4):495-504
references.pmid: 12201634
references.citation: Neuroscience. 1991;42(2):335-50
references.pmid: 1832750
references.citation: Eur J Neurosci. 2009 Jan;29(2):377-87
references.pmid: 19200240
references.citation: Brain Res. 2010 Apr 22;1326:143-51
references.pmid: 20188711
references.citation: Hippocampus. 2006;16(2):103-13
references.pmid: 16261555
references.citation: PLoS One. 2011 Jan 19;6(1):e15982
references.pmid: 21283812
references.citation: Science. 2011 Dec 9;334(6061):1415-20
references.pmid: 22052975
references.citation: Hippocampus. 2005;15(4):418-26
references.pmid: 15669102
references.citation: PLoS One. 2012;7(9):e45720
references.pmid: 23029199
references.citation: Neurosci Biobehav Rev. 2006;30(2):188-202
references.pmid: 16120461
references.citation: Trends Neurosci. 2013 Jan;36(1):23-31
references.pmid: 23260015
references.citation: Behav Brain Res. 2006 Apr 3;168(2):289-98
references.pmid: 16413066
references.citation: Hippocampus. 2009 Jan;19(1):20-32
references.pmid: 18651617
references.citation: Neurobiol Learn Mem. 2008 Oct;90(3):537-43
references.pmid: 18678265
references.citation: Physiol Rev. 2010 Apr;90(2):419-63
references.pmid: 20393190
references.citation: J Exp Psychol Anim Behav Process. 2008 Apr;34(2):202-22
references.pmid: 18426304
references.citation: J Exp Psychol Anim Behav Process. 1982 Apr;8(2):131-41
references.pmid: 7069375
references.citation: Learn Mem. 2010 May 26;17(6):289-96
references.pmid: 20504949
references.citation: Neurobiol Learn Mem. 2011 Sep;96(2):181-91
references.pmid: 21514394
references.citation: J Neurosci. 2009 Apr 8;29(14):4346-50
references.pmid: 19357262
references.citation: Genes Brain Behav. 2009 Apr;8(3):320-9
references.pmid: 19191880
references.citation: Neuropsychopharmacology. 2011 Jan;36(2):529-38
references.pmid: 20962768
references.citation: Hippocampus. 2009 Jan;19(1):33-44
references.pmid: 18683846
references.citation: Synapse. 2004 Jan;51(1):32-58
references.pmid: 14579424
references.citation: J Comp Physiol Psychol. 1961 Apr;54:149-53
references.pmid: 13751034
references.citation: Hippocampus. 2013 Jul;23(7):625-33
references.pmid: 23520022
references.citation: Neurosci Biobehav Rev. 2004 Nov;28(7):771-84
references.pmid: 15555683
references.citation: Neurobiol Learn Mem. 2013 Nov;106:316-23
references.pmid: 23747568
references.citation: Eur J Neurosci. 2008 Apr;27(8):1923-32
references.pmid: 18412613
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11489-94
references.pmid: 17592139
references.citation: J Neurosci. 2013 Jun 26;33(26):10910-4
references.pmid: 23804110
references.citation: Hippocampus. 2005;15(5):665-74
references.pmid: 15959918
references.citation: Behav Neurosci. 2005 Jun;119(3):834-8
references.pmid: 15998205
references.citation: J Neurosci. 2004 Feb 11;24(6):1288-95
references.pmid: 14960599
references.citation: Learn Mem. 2011 Oct 25;18(11):728-32
references.pmid: 22028394
references.citation: Neurobiol Learn Mem. 2007 Jan;87(1):86-92
references.pmid: 16904919
references.citation: Neurobiol Learn Mem. 2006 Nov;86(3):311-21
references.pmid: 16774840
references.citation: Brain Res. 2004 Jan 2;995(1):55-65
references.pmid: 14644471
references.citation: Neuroscience. 2006 Sep 29;142(1):1-20
references.pmid: 16887277
references.citation: Neuron. 2000 Feb;25(2):473-80
references.pmid: 10719900
references.citation: Neurobiol Learn Mem. 2012 May;97(4):452-64
references.pmid: 22469748
references.citation: Learn Mem. 1999 Sep-Oct;6(5):478-90
references.pmid: 10541468
references.citation: Behav Neurosci. 2007 Feb;121(1):50-62
references.pmid: 17324050
references.citation: Neurosci Biobehav Rev. 2004 Nov;28(7):675-85
references.pmid: 15555677
references.citation: Neurobiol Learn Mem. 2006 Jul;86(1):72-81
references.pmid: 16504548
references.citation: Mol Brain. 2012 Feb 03;5:6
references.pmid: 22304729
references.citation: Annu Int Conf IEEE Eng Med Biol Soc. 2007;2007:2480-4
references.pmid: 18002497
references.citation: J Exp Psychol Anim Behav Process. 2005 Jan;31(1):31-9
references.pmid: 15656725
references.citation: Neurobiol Learn Mem. 2004 Sep;82(2):65-70
references.pmid: 15341790
references.citation: Learn Behav. 2005 Nov;33(4):437-43
references.pmid: 16573214
references.citation: Brain Res Rev. 2011 Jan 1;65(2):124-49
references.pmid: 20837060
references.citation: Annu Rev Psychol. 2005;56:207-34
references.pmid: 15709934
references.citation: J Exp Psychol Anim Behav Process. 2012 Oct;38(4):369-80
references.pmid: 22905828
references.citation: Ann N Y Acad Sci. 2003 Apr;985:125-34
references.pmid: 12724154
references.citation: Ann N Y Acad Sci. 1984;423:211-27
references.pmid: 6588787
references.citation: Learn Mem. 2013 May 17;20(6):336-43
references.pmid: 23685809
references.citation: Alcohol Clin Exp Res. 2004 Oct;28(10):1433-6
references.pmid: 15597074
references.citation: J Neurosci. 2007 May 23;27(21):5757-65
references.pmid: 17522319
references.citation: Brain Res Rev. 2006 Aug;51(2):145-60
references.pmid: 16530842
references.citation: Learn Mem. 2004 Mar-Apr;11(2):205-12
references.pmid: 15054136
references.citation: Neuron. 1999 Jun;23(2):229-32
references.pmid: 10399930
references.citation: Behav Brain Res. 2013 Jan 15;237:348-56
references.pmid: 23069005
references.citation: Hippocampus. 2000;10(6):739-51
references.pmid: 11153719
references.citation: Hippocampus. 2005;15(3):333-9
references.pmid: 15523611
references.citation: Biol Psychiatry. 1999 May 15;45(10):1237-58
references.pmid: 10349031
references.citation: Learn Mem. 2007 Sep 05;14(9):597-605
references.pmid: 17823243
references.citation: Behav Neurosci. 2002 Feb;116(1):37-47
references.pmid: 11895181
references.citation: Neural Plast. 2008;2008:658323
references.pmid: 18670635
references.citation: Hippocampus. 2007;17(6):462-70
references.pmid: 17372979
references.citation: J Neurosci. 2009 Jun 24;29(25):8087-93
references.pmid: 19553448
references.citation: J Neurosci. 1999 Dec 15;19(24):10869-76
references.pmid: 10594068
references.citation: Ann Neurosci. 2010 Jul;17(3):136-41
references.pmid: 25205891
references.citation: Behav Brain Res. 2003 Feb 17;139(1-2):197-213
references.pmid: 12642189
references.citation: J Exp Psychol Anim Behav Process. 1989 Oct;15(4):295-310
references.pmid: 2794867
references.citation: Neurosci Biobehav Rev. 2004 May;28(3):273-83
references.pmid: 15225971
references.citation: Behav Processes. 2014 Jan;101:4-14
references.pmid: 23751257
references.citation: Brain Res. 2013 Feb 1;1493:48-67
references.pmid: 23178699
references.citation: Learn Mem. 2009 Apr 20;16(5):279-88
references.pmid: 19380710
references.citation: Hippocampus. 1998;8(6):638-46
references.pmid: 9882021
references.citation: Trends Neurosci. 2008 Feb;31(2):105-12
references.pmid: 18199490
references.citation: J Neurosci. 2005 Aug 10;25(32):7385-92
references.pmid: 16093389
references.citation: Behav Neurosci. 1990 Apr;104(2):243-52
references.pmid: 2346619
references.citation: Brain Struct Funct. 2007 Sep;212(2):149-79
references.pmid: 17717690
references.citation: J Comp Physiol Psychol. 1964 Jun;57:373-80
references.pmid: 14155374
references.citation: Psychophysiology. 1966 Oct;3(2):108-14
references.pmid: 5927826
references.citation: J Neurosci. 2012 Jan 18;32(3):1082-95
references.pmid: 22262906
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13087-92
references.pmid: 14555761
references.citation: Behav Neurosci. 2005 Aug;119(4):1011-22
references.pmid: 16187829
references.citation: Learn Mem. 2013 May 15;20(6):290-4
references.pmid: 23676200
references.citation: Behav Brain Res. 2004 Nov 5;155(1):167-73
references.pmid: 15325790
references.citation: J Exp Psychol Anim Behav Process. 2010 Apr;36(2):281-95
references.pmid: 20384407
references.citation: J Neurodev Disord. 2009 Sep;1(3):224-36
references.pmid: 19816534
references.citation: Hippocampus. 2012 Jul;22(7):1528-39
references.pmid: 22180082
references.citation: Neurobiol Aging. 2011 Aug;32(8):1452-65
references.pmid: 19833411
references.citation: Neuroimage. 2000 Dec;12(6):688-97
references.pmid: 11112400
references.citation: J Comp Physiol Psychol. 1968 Dec;66(3):673-8
references.pmid: 5721495
references.citation: Behav Neurosci. 2005 Dec;119(6):1496-510
references.pmid: 16420154
references.citation: Behav Neurosci. 2005 Oct;119(5):1396-402
references.pmid: 16300446
references.citation: Behav Neurosci. 2005 Feb;119(1):164-79
references.pmid: 15727522
references.citation: Behav Brain Res. 2008 Oct 10;192(2):264-8
references.pmid: 18514922
references.citation: Eur J Neurosci. 2003 May;17(9):1953-63
references.pmid: 12752795
references.citation: Behav Neurosci. 2012 Apr;126(2):258-69
references.pmid: 22352787
references.citation: Microsc Res Tech. 2000 Oct 1;51(1):45-53
references.pmid: 11002352
references.citation: Behav Brain Res. 2005 Feb 10;157(1):63-9
references.pmid: 15617772
references.citation: Hippocampus. 2012 Oct;22(10):2068-79
references.pmid: 22903623
references.citation: Neurobiol Learn Mem. 2007 Oct;88(3):359-68
references.pmid: 17560814