title: Temporal factors control hippocampal contributions to fear renewal after extinction.
abstract: Fear can be extinguished by repeated exposure to a cue that signals threat. However, extinction does not erase fear, as an extinguished cue presented in a context distinct from that of extinction results in renewed fear of that cue. The hippocampus, which is involved in the formation of contextual representations, is a natural candidate structure for investigations into the neural circuitry underlying fear renewal. Thus far, studies examining the necessity of the hippocampus for fear renewal have produced mixed results. We isolated the conditions under which the hippocampus may be required for renewal. Rats received lesions of the dorsal hippocampus either prior to tone fear conditioning or following extinction. Fear renewal was measured using discrete tone presentations or a long, continuous tone. The topography of fear responding at test was assessed by comparing "early" and "sustained" renewal, where early fear was determined by freezing to the first discrete tone or the equivalent initial segment of a continuous tone and sustained fear was determined by freezing averaged across all discrete tones or the entire continuous tone. We found that following pretraining damage of the hippocampus, early renewal remained intact regardless of lesion condition. However, sustained renewal only persisted in discrete, but not continuous, tone-tested animals. A more extensive analysis of the topography of fear responding revealed that the disruption of renewal was generated when the tone duration at test began to violate that used during extinction, suggesting that the hippocampus is sensitive to mismatches in CS-duration. Postextinction lesions resulted in an overall reduction of fear renewal. This pattern of results is consistent with those observed for contextual fear conditioning, wherein animals display a resistance to anterograde amnesia despite the presence of a strong retrograde amnesia for the same contextual information. Furthermore, the data support a role for the hippocampus in sustaining renewal when the CS duration at test does not match that used during extinction.
authors: Department of Psychology and Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095-1563, USA.
authors: Moriel
authors: M
authors: Zelikowsky
authors: Daniel L
authors: DL
authors: Pham
authors: Michael S
authors: MS
authors: Fanselow
references: Curr Opin Neurobiol. 2000 Apr;10(2):260-5
references: 10753789
references: Behav Brain Res. 2000 Jun 1;110(1-2):73-81
references: 10802305
references: Trends Cogn Sci. 2010 Jan;14(1):7-15
references: 19939724
references: Psychol Bull. 1993 Jul;114(1):80-99
references: 8346330
references: Behav Brain Res. 2008 Dec 12;194(2):201-6
references: 18692093
references: Behav Brain Res. 1997 Nov;88(2):261-74
references: 9404635
references: J Exp Psychol Anim Behav Process. 2004 Jul;30(3):163-76
references: 15279508
references: J Comp Physiol Psychol. 1968 Dec;66(3):606-12
references: 5721489
references: Eur J Neurosci. 2009 Apr;29(8):1692-700
references: 19419430
references: Hippocampus. 2005;15(6):808-14
references: 16010664
references: Behav Neurosci. 2000 Apr;114(2):227-40
references: 10832785
references: J Neurosci. 2001 Mar 1;21(5):1720-6
references: 11222661
references: J Exp Psychol Anim Behav Process. 1979 Oct;5(4):368-78
references: 528893
references: Learn Mem. 2004 Sep-Oct;11(5):598-603
references: 15466314
references: Pavlov J Biol Sci. 1980 Oct-Dec;15(4):177-82
references: 7208128
references: Behav Brain Res. 1989 Aug 1;34(1-2):97-109
references: 2765175
references: Learn Behav. 2007 Feb;35(1):11-8
references: 17557387
references: Science. 1992 May 1;256(5057):675-7
references: 1585183
references: J Exp Psychol Anim Behav Process. 1993 Oct;19(4):327-41
references: 8228832
references: Nat Rev Neurosci. 2004 May;5(5):361-72
references: 15100719
references: Learn Mem. 2005 May-Jun;12(3):270-6
references: 15930505
references: Learn Mem. 2004 Sep-Oct;11(5):485-94
references: 15466298
references: Hippocampus. 2006;16(2):174-82
references: 16358312
references: Neurosci Biobehav Rev. 2004 Nov;28(7):675-85
references: 15555677
references: Biol Psychiatry. 2002 Nov 15;52(10):976-86
references: 12437938
references: J Neurosci. 2005 Sep 28;25(39):8978-87
references: 16192388
references: Behav Neurosci. 1995 Oct;109(5):828-36
references: 8554708
references: Hippocampus. 2004;14(3):301-10
references: 15132429
references: J Neurosci. 1999 Feb 1;19(3):1106-14
references: 9920672
references: Psychol Rev. 1992 Apr;99(2):195-231
references: 1594723
references: Behav Processes. 2006 Feb 28;71(2-3):307-17
references: 16412585
references: J Neurosci. 2006 May 17;26(20):5484-91
references: 16707800
references: Behav Processes. 2010 May;84(1):412-20
references: 20067824
references: Behav Res Ther. 2008 Jan;46(1):5-27
references: 18005936
references: Learn Mem. 2008 Apr 03;15(4):244-51
references: 18391185
references: Hippocampus. 2008;18(7):640-54
references: 18306286