title: Learning not to fear: neural correlates of learned safety.
abstract: The ability to recognize and properly respond to instances of protection from impending danger is critical for preventing chronic stress and anxiety-central symptoms of anxiety and affective disorders afflicting large populations of people. Learned safety encompasses learning processes, which lead to the identification of episodes of security and regulation of fear responses. On the basis of insights into the neural circuitry and molecular mechanisms involved in learned safety in mice and humans, we describe learned safety as a tool for understanding neural mechanisms involved in the pathomechanisms of specific affective disorders. This review summarizes our current knowledge on the neurobiological underpinnings of learned safety and discusses potential applications in basic and translational neurosciences.
authors: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Eryan
authors: E
authors: Kong
authors: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Francisco J
authors: FJ
authors: Monje
authors: 1] Department of Neuroscience, Columbia University, New York, NY, USA [2] fMRI Research Center, Columbia University, New York, NY, USA [3] Department of Radiology, Columbia University, New York, NY, USA [4] Department of Psychology, Columbia University, New York, NY, USA.
authors: Joy
authors: J
authors: Hirsch
authors: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Daniela D
authors: DD
authors: Pollak
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D005239:Fear; D006801:Humans; D007858:Learning / Q000502:physiology*
references: J Neurosci. 2008 Dec 10;28(50):13703-11
references: 19074043
references: J Neurosci. 2012 May 9;32(19):6444-55
references: 22573667
references: Annu Rev Neurosci. 2000;23:155-84
references: 10845062
references: Prog Neurobiol. 2011 Apr;93(4):522-48
references: 21420466
references: Neuroimage. 2007 Oct 15;38(1):171-83
references: 17703956
references: Neuropsychopharmacology. 2005 Jan;30(1):17-26
references: 15257308
references: J Exp Psychol. 1968 Feb;76(2):171-80
references: 5636557
references: J Comp Physiol Psychol. 1969 Apr;67(4):504-9
references: 5787403
references: J Neurosci. 1992 Nov;12(11):4501-9
references: 1331362
references: Behav Neurosci. 1995 Jun;109(3):379-87
references: 7662148
references: Depress Anxiety. 2013 Mar;30(3):217-24
references: 22907890
references: Dev Cogn Neurosci. 2011 Jan;1(1):77-87
references: 21037982
references: Front Behav Neurosci. 2013 Apr 10;7:30
references: 23596403
references: Learn Mem. 2004 Sep-Oct;11(5):544-8
references: 15466306
references: Cereb Cortex. 2011 Sep;21(9):1954-62
references: 21263037
references: Philos Trans R Soc Lond B Biol Sci. 2007 May 29;362(1481):787-99
references: 17403643
references: J Neurosci. 2008 Nov 5;28(45):11517-25
references: 18987188
references: Behav Neurosci. 1997 Aug;111(4):712-26
references: 9267649
references: Neuron. 2008 Jul 31;59(2):298-310
references: 18667157
references: Biol Psychol. 2006 Jul;73(1):61-71
references: 16476517
references: Behav Neurosci. 1997 Jun;111(3):476-86
references: 9189262
references: Ann N Y Acad Sci. 1999 Jun 29;877:281-91
references: 10415655
references: J Affect Disord. 2005 Sep;88(1):79-86
references: 16033700
references: Nat Protoc. 2010 May;5(5):954-62
references: 20431541
references: Proc Natl Acad Sci U S A. 2010 May 18;107(20):9418-23
references: 20439732
references: Neuron. 2005 Oct 20;48(2):175-87
references: 16242399
references: Learn Mem. 2004 Sep-Oct;11(5):611-6
references: 15466316
references: Nat Rev Neurosci. 2004 Nov;5(11):844-52
references: 15496862
references: Pharmacol Biochem Behav. 2011 Aug;99(2):217-28
references: 21256147
references: Biol Psychol. 2006 Jul;73(1):49-60
references: 16500019
references: Biol Psychiatry. 2011 Sep 1;70(5):458-64
references: 21684526
references: Behav Processes. 2004 May 31;66(2):153-60
references: 15110917
references: Neuropsychopharmacology. 2008 Jan;33(1):56-72
references: 17882236
references: J Neurosci. 2004 Sep 8;24(36):7958-63
references: 15356210
references: J Neurosci. 2000 Aug 15;20(16):6225-31
references: 10934272
references: Neuroscience. 2007 Feb 9;144(3):788-96
references: 17140740
references: Trends Neurosci. 2013 Jan;36(1):23-31
references: 23260015
references: Depress Anxiety. 2009;26(11):1018-26
references: 19691032
references: Sleep. 2008 Apr;31(4):497-503
references: 18457237
references: Ann Med. 2010 Mar;42(2):115-22
references: 20121549
references: Behav Neurosci. 2012 Jun;126(3):392-403
references: 22642884
references: Neuron. 2006 Apr 6;50(1):127-43
references: 16600861
references: Neuron. 2012 Nov 21;76(4):804-12
references: 23177964
references: Eur J Neurosci. 2005 Feb;21(4):1077-80
references: 15787712
references: Learn Mem. 2009 Feb 17;16(3):187-92
references: 19228588
references: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12348-53
references: 15297618
references: J Neurosci. 1999 Jan 1;19(1):420-30
references: 9870970
references: Mol Brain. 2009 Jan 13;2:1
references: 19138433
references: Behav Brain Res. 2003 Oct 17;145(1-2):89-98
references: 14529808
references: Mol Psychiatry. 2007 Jul;12(7):656-70
references: 17264839
references: Behav Processes. 2012 May;90(1):49-57
references: 22465469
references: Biol Psychiatry. 2000 Mar 15;47(6):512-9
references: 10715357
references: Biol Psychiatry. 2005 Jun 15;57(12):1559-64
references: 15953493
references: Trends Cogn Sci. 2011 Feb;15(2):85-93
references: 21167765
references: Biol Psychiatry. 1994 Apr 1;35(7):431-9
references: 8018793
references: Behav Neurosci. 1995 Aug;109(4):681-8
references: 7576212
references: J Neurosci. 2001 Mar 15;21(6):RC135
references: 11245704
references: Depress Anxiety. 2010 Mar;27(3):244-51
references: 20143428
references: Neurosci Lett. 1993 Nov 26;163(1):109-13
references: 8295722
references: Nature. 1997 Dec 11;390(6660):604-7
references: 9403688
references: Am J Psychiatry. 2011 Sep;168(9):968-78
references: 21632648
references: Physiol Behav. 1994 Oct;56(4):785-8
references: 7800749
references: Mol Psychiatry. 2007 Feb;12(2):120-50
references: 17160066
references: Cereb Cortex. 2008 Dec;18(12):2941-51
references: 18424777
references: Annu Rev Neurosci. 1992;15:353-75
references: 1575447
references: Cortex. 2013 Jul-Aug;49(7):1884-91
references: 23020899
references: Neuron. 2005 Apr 21;46(2):309-20
references: 15848808
references: PLoS One. 2013;8(2):e51149
references: 23468832
references: J Comp Neurol. 1998 Oct 5;399(4):440-68
references: 9741477
references: Biol Psychiatry. 2006 Aug 15;60(4):352-60
references: 16616731
references: Pharmacol Biochem Behav. 1984 Jan;20(1):39-44
references: 6538045
references: Neuropharmacology. 2012 Feb;62(2):695-704
references: 21377482
references: Biol Psychiatry. 1995 Sep 15;38(6):378-85
references: 8547457
references: Nat Neurosci. 2006 Jul;9(7):870-2
references: 16783370
references: Behav Brain Res. 2003 Jun 16;142(1-2):115-24
references: 12798272
references: Neuropharmacology. 2013 Jan;64:414-23
references: 22722028
references: Trends Cogn Sci. 2012 Mar;16(3):147-56
references: 22310704
references: Neuron. 2008 Oct 9;60(1):149-61
references: 18940595
references: Ann N Y Acad Sci. 1999 Jun 29;877:309-38
references: 10415657
references: Behav Brain Res. 2003 Nov 30;146(1-2):121-30
references: 14643465
references: Anxiety. 1994;1(1):13-21
references: 9160541
references: Behav Neurosci. 2001 Aug;115(4):764-75
references: 11508716
references: J Comp Physiol Psychol. 1971 Apr;75(1):77-81
references: 5559222
references: Trends Neurosci. 2012 Jan;35(1):24-35
references: 21798604
references: Ann N Y Acad Sci. 2006 Jul;1071:67-79
references: 16891563
references: Psychophysiology. 2001 Sep;38(5):807-15
references: 11577904
references: J Neurosci. 2009 Oct 28;29(43):13532-42
references: 19864566
references: Am J Psychiatry. 2004 Nov;161(11):1957-66
references: 15514393
references: J Affect Disord. 2000 Dec;61(3):225-40
references: 11163424
references: Eur J Neurosci. 2007 Nov;26(9):2654-60
references: 17970744
references: Am J Psychiatry. 1996 Jan;153(1):64-8
references: 8540594
references: Genes Brain Behav. 2012 Jul;11(5):503-12
references: 22530815
references: Proc Natl Acad Sci U S A. 2012 May 29;109(22):8764-9
references: 22586125
references: Arch Gen Psychiatry. 2001 Nov;58(11):1005-14
references: 11695946
references: Behav Res Ther. 2009 Feb;47(2):111-8
references: 19027893
references: Neurobiol Learn Mem. 2008 Jul;90(1):200-16
references: 18434217
references: Eur J Neurosci. 2000 Nov;12(11):4047-54
references: 11069601
references: Mol Psychiatry. 2008 Dec;13(12):1070-8
references: 18679406
references: Neuron. 1995 Jul;15(1):127-36
references: 7619517
references: Neuropsychopharmacology. 2011 Jan;36(1):360-1
references: 21116254