Fear conditioning induces distinct patterns of gene expression in lateral amygdala.
The lateral nucleus of the amygdala (LA) has been implicated in the formation of long-term associative memory (LTM) of stimuli associated with danger through fear conditioning. The current study aims to detect genes that are expressed in LA following associative fear conditioning. Using oligonucleotide microarrays, we monitored gene expression in rats subjected to paired training where a tone co-terminates with a footshock, or unpaired training where the tone and footshock are presented in a non-overlapping manner. The paired protocol consistently leads to auditory fear conditioning memory formation, whereas the unpaired protocol does not. When the paired group was compared with the unpaired group 5 h after training, the expression of genes coding for the limbic system-associated membrane protein (Lsamp), kinesin heavy chain member 2 (Kif2), N-ethylmaleimide-sensitive fusion protein (NSF) and Hippocalcin-like 4 protein (Hpcal4) was higher in the paired group. These genes encode proteins that regulate neuronal axonal morphology (Lsamp, Kif2), presynaptic vesicle cycling and release (Hpcal4 and NSF), and AMPA receptor maintenance in synapses (NSF). Quantitative real-time PCR (qPCR) showed that Kif2 and Lsamp are expressed hours following fear conditioning but minutes after unpaired training. Hpcal4 is induced by paired stimulation only 5 h after the training. These results show that fear conditioning induces a unique temporal activation of molecular pathways involved in regulating synaptic transmission and axonal morphology in LA, which is different from non-associative stimulation.
Lamprecht
R
R
Department of Neurobiology and Ethology, University of Haifa, Haifa, Israel. rlamp@research.haifa.ac.il
Dracheva
S
S
Assoun
S
S
LeDoux
J E
JE
D000161:Acoustic Stimulation; D000679:Amygdala / Q000033:anatomy & histology / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D003213:Conditioning, Psychological / Q000502:physiology*; D004558:Electric Stimulation; D005239:Fear / Q000502:physiology*; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D016547:Kinesins / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics*; D013570:Synaptic Membranes / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors
D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C509805:KIF2A protein, human; D009419:Nerve Tissue Proteins; C095362:limbic system-associated membrane protein; D016547:Kinesins; D052066:N-Ethylmaleimide-Sensitive Proteins; C498737:Nsf protein, rat
Brain Res. 2008 Jun 12;1214:23-34
18462708
Behav Neurosci. 1999 Apr;113(2):276-82
10357452
Learn Mem. 2006 Mar-Apr;13(2):135-42
16547164
Trends Neurosci. 2001 Sep;24(9):540-6
11506888
Eur J Neurosci. 2003 Dec;18(11):3080-8
14656303
Neuron. 2004 Sep 30;44(1):75-91
15450161
Brain Res. 1991 Nov 29;565(2):349-52
1842702
Cell. 2003 Jul 25;114(2):229-39
12887924
Brain Res. 2006 Jul 19;1100(1):21-31
16769038
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
12184808
Neuroscientist. 2005 Feb;11(1):75-88
15632280
Curr Opin Neurobiol. 1992 Jun;2(3):312-6
1322751
Mol Psychiatry. 2001 Jan;6(1):13-34
11244481
Nat Rev Neurosci. 2007 Mar;8(3):182-93
17311005
Learn Mem. 2001 Jul-Aug;8(4):209-19
11533224
Nature. 1993 Jan 7;361(6407):31-9
8421494
Learn Mem. 2001 Sep-Oct;8(5):229-42
11584069
J Neurosci. 2000 Sep 15;20(18):RC96
10974093
Brain Res Bull. 2005 Sep 30;67(1-2):1-12
16140156
EMBO J. 2006 Jun 21;25(12):2698-709
16724110
Curr Opin Neurobiol. 2004 Oct;14(5):564-73
15464889
Physiol Rev. 2003 Jul;83(3):803-34
12843409
FEBS Lett. 2007 May 22;581(11):2140-9
17397838
Nature. 1993 Nov 11;366(6451):156-8
7901765
J Neurosci. 2005 Jul 27;25(30):7071-80
16049184
Mol Cell Neurosci. 2005 Oct;30(2):197-206
16095914
Neuron. 1994 Mar;12(3):605-13
8155322
Nature. 1986 Jul 31-Aug 6;322(6078):419-22
2874497
Neuron. 2002 Nov 14;36(4):727-38
12441060
Annu Rev Psychol. 2005;56:207-34
15709934
Nat Rev Neurosci. 2004 Jan;5(1):45-54
14708003
Neuron. 1999 Jun;23(2):229-32
10399930
Behav Brain Res. 2008 Apr 9;188(2):380-90
18199495
J Neurosci. 2002 Sep 15;22(18):7892-902
12223542
Neuron. 2005 Sep 15;47(6):783-6
16157273
Neuron. 2005 Apr 21;46(2):309-20
15848808
Curr Opin Neurobiol. 2000 Apr;10(2):266-73
10753792
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2145-50
14766980
Learn Mem. 2008 Oct 02;15(10):747-55
18832561
Annu Rev Neurosci. 2000;23:649-711
10845078
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13445-52
8942955
Science. 2001 Nov 2;294(5544):1030-8
11691980
J Neurosci. 1988 Dec;8(12):4653-61
3199199
Neuron. 2002 Apr 11;34(2):221-33
11970864
Neuron. 2008 Oct 9;60(1):149-61
18940595
Neuron. 1995 Aug;15(2):287-97
7646886
J Cell Sci. 2003 Apr 1;116(Pt 7):1209-17
12615964
Nat Rev Neurosci. 2002 Dec;3(12):921-31
12461549
Genes Brain Behav. 2004 Apr;3(2):80-9
15005716
Annu Rev Neurosci. 2000;23:155-84
10845062
Annu Rev Biophys Biomol Struct. 2001;30:157-71
11340056
Neurobiol Learn Mem. 2007 Nov;88(4):424-34
17613254
Neuron. 1989 Nov;3(5):551-61
2642010
J Cell Biol. 1997 Aug 11;138(3):657-69
9245793
Psychol Bull. 1984 Nov;96(3):518-59
6096908
J Neurosci. 2005 Jul 27;25(30):7062-70
16049183