Graded fear generalization enhances the level of cfos-positive neurons specifically in the basolateral amygdala.
Fear is an important emotional reaction in response to threatening stimuli and is important for survival. However, when fear occurs in inappropriate circumstances, it can lead to pathological conditions including an increased vulnerability for developing anxiety disorders such as posttraumatic stress disorder (PTSD). Patients with PTSD generalize fear to contexts or to environments that are not associated with the trauma. We sought to explore if increasing the level of dissimilarity relative to the context in which mice learn fear results in changes in the level of fear responding to the new context. We also determined with this procedure if the number of cells expressing the immediate early gene cfos changes with the corresponding level of expressed fear within brain regions known to be important in modulating fear, including the basolateral amygdala (BLA) and hippocampus. Our results indicate that mice that were tested in increasingly different contexts showed significantly different levels of fear responses. Freezing level was higher in the context most similar to the acquisition context than the one that was highly different. The level of cfos within the BLA, but not hippocampus, was also significantly different between the test contexts, with higher levels in the somewhat similar compared with the most different context. Overall, these results highlight the BLA as a critical region in the node of fear circuitry for modulating fear generalization. © 2016 Wiley Periodicals, Inc.
Department of Psychiatry, University of California, Los Angeles, Los Angeles, California.|Department of Psychology, University of California, Los Angeles, Los Angeles, California.
Abha K
AK
Rajbhandari
Department of Psychology, University of California, Los Angeles, Los Angeles, California.
Ruoyan
R
Zhu
Department of Psychology, University of California, Los Angeles, Los Angeles, California.
Cora
C
Adling
Department of Psychiatry, University of California, Los Angeles, Los Angeles, California.|Department of Psychology, University of California, Los Angeles, Los Angeles, California.
Michael S
MS
Fanselow
Department of Psychiatry, University of California, Los Angeles, Los Angeles, California. jwashchek@mednet.ucla.edu.
James A
JA
Waschek
D000679:Amygdala / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D003213:Conditioning, Psychological; D005239:Fear / Q000523:psychology*; D005793:Generalization, Psychological; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000523:psychology
D016760:Proto-Oncogene Proteins c-fos
amygdala; fear conditioning; fear generalization
J Exp Anal Behav. 1988 Nov;50(3):361-74
3209954
J Abnorm Psychol. 1999 Feb;108(1):134-42
10066999
Science. 2007 Jul 6;317(5834):94-9
17556551
Soc Cogn Affect Neurosci. 2014 Aug;9(8):1134-42
23748500
Neuropsychopharmacology. 2010 Jan;35(1):169-91
19625997
Ann N Y Acad Sci. 2003 Apr;985:125-34
12724154
Neuron. 1996 Feb;16(2):237-40
8789938
Neurosci Biobehav Rev. 1999 May;23(5):743-60
10392663
Psychol Rev. 1998 Apr;105(2):325-50
9577241
J Neurosci. 2014 Jun 18;34(25):8462-6
24948801
J Neurosci. 1988 Jul;8(7):2517-29
2854842
Nat Rev Neurosci. 2012 Nov;13(11):769-87
23047775
Annu Rev Neurosci. 1992;15:353-75
1575447
Neuron. 1999 Jun;23(2):229-32
10399930
Neuron. 2007 Oct 4;56(1):19-32
17920012
Trends Neurosci. 2015 Mar;38(3):158-66
25583269
Nature. 2011 Feb 24;470(7335):492-7
21350482
Cell Mol Neurobiol. 2003 Oct;23(4-5):727-38
14514027
Behav Neurosci. 2004 Feb;118(1):253-7
14979804
Cell. 2012 Mar 30;149(1):188-201
22365813
Science. 1995 Aug 25;269(5227):1115-8
7652558
Biol Psychiatry. 2015 Sep 1;78(5):E15-27
26238379
Hippocampus. 2001;11(1):8-17
11261775
Psychiatr Clin North Am. 2002 Jun;25(2):271-93
12136501
Cold Spring Harb Perspect Biol. 2015 Nov 09;8(1):a021717
26552417
Behav Brain Res. 2002 Aug 21;134(1-2):299-306
12191817
Depress Anxiety. 2010 Mar;27(3):244-51
20143428
Neurosci Biobehav Rev. 2006;30(2):188-202
16120461
J Neurosci. 1990 Apr;10(4):1062-9
2329367
Pavlov J Biol Sci. 1980 Oct-Dec;15(4):177-82
7208128
Front Behav Neurosci. 2015 May 27;9:112
26074792
Ann N Y Acad Sci. 2003 Dec;1008:112-21
14998877
Biol Psychiatry. 2011 Mar 15;69(6):556-63
21035787
Behav Brain Res. 2000 Jun 1;110(1-2):73-81
10802305
Annu Rev Neurosci. 2000;23:155-84
10845062
J Clin Psychiatry. 2001;62 Suppl 17:41-6
11495096
Am J Psychiatry. 2010 Jun;167(6):648-62
20231322
Science. 1992 May 1;256(5057):675-7
1585183
Arch Gen Psychiatry. 1995 Dec;52(12):1048-60
7492257
J Comp Neurol. 2016 Dec 15;524(18):3827-3848
27197019
J Psychiatr Res. 2013 Dec;47(12):1991-7
24090716
Biol Psychol. 2006 Jul;73(1):61-71
16476517
Acta Psychol (Amst). 2008 Mar;127(3):567-80
18226795