title: Spontaneous recovery of fear reverses extinction-induced excitability of infralimbic neurons.
abstract: In rodents, the infralimbic (IL) region of the medial prefrontal cortex plays a key role in the recall of fear extinction. Previously we showed that fear conditioning decreases the intrinsic excitability of IL neurons, and that fear extinction reverses the depressed excitability. In the current study, we examined the time course of the extinction-induced changes in adolescent rats. Immediately after extinction, IL neurons continued to show depressed excitability. However 4 hours after extinction, IL neurons showed an increase in evoked spikes that correlated with a reduced fast afterhyperpolarizing potential. This suggests that acquisition of fear extinction induces an increase in spike firing 4 hours later, during the consolidation of extinction. We also examined IL excitability in a group of rats that showed spontaneous recovery of fear 17 days after extinction (SR group). Similar to neurons after fear conditioning, IL neurons from the SR group showed depressed intrinsic excitability compared to neurons 4 hours after extinction, suggesting that extinction-induced enhancement in intrinsic excitability decreases with time reverting back to a depressed state. These results suggest that plasticity in IL contributes to the spontaneous recovery of fear and preventing this depression of IL excitability could prolong fear extinction.
authors.affiliation: Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce, Puerto Rico.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cruz
authors.affiliation: Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce, Puerto Rico.
authors.forename: Ana V
authors.initials: AV
authors.lastname: López
authors.affiliation: Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce, Puerto Rico.
authors.forename: James T
authors.initials: JT
authors.lastname: Porter
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000523:psychology*; D008032:Limbic System / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D017207:Rats, Sprague-Dawley
references.citation: J Neurosci. 2010 Sep 15;30(37):12379-86
references.pmid: 20844133
references.citation: Nature. 2008 Jul 31;454(7204):642-5
references.pmid: 18615014
references.citation: J Neurosci. 2008 Apr 9;28(15):4028-36
references.pmid: 18400902
references.citation: Eur J Neurosci. 2010 Feb;31(4):599-612
references.pmid: 20384807
references.citation: Neuropsychopharmacology. 2011 Jan;36(2):529-38
references.pmid: 20962768
references.citation: Biol Psychiatry. 2009 Dec 15;66(12):1075-82
references.pmid: 19748076
references.citation: Curr Opin Neurobiol. 2010 Apr;20(2):231-5
references.pmid: 20303254
references.citation: Cereb Cortex. 2011 Mar;21(3):727-35
references.pmid: 20705895
references.citation: Nature. 2002 Nov 7;420(6911):70-4
references.pmid: 12422216
references.citation: Curr Opin Neurobiol. 2012 Aug;22(4):717-23
references.pmid: 22424846
references.citation: Neuron. 2013 Dec 18;80(6):1491-507
references.pmid: 24290204
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16318-23
references.pmid: 22988092
references.citation: Neurosci Biobehav Rev. 2012 Aug;36(7):1773-802
references.pmid: 22230704
references.citation: Neuropsychopharmacology. 2010 Sep;35(10):2134-42
references.pmid: 20592716
references.citation: J Neurosci. 2013 Apr 24;33(17):7184-93
references.pmid: 23616528
references.citation: J Neurosci. 2002 Jan 15;22(2):577-83
references.pmid: 11784805
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20955-60
references.pmid: 18165656
references.citation: Annu Rev Psychol. 2012;63:129-51
references.pmid: 22129456
references.citation: Neuropsychopharmacology. 2008 Jan;33(1):56-72
references.pmid: 17882236
references.citation: Neuropsychopharmacology. 2011 Oct;36(11):2276-85
references.pmid: 21750582
references.citation: Learn Mem. 2002 Nov-Dec;9(6):402-7
references.pmid: 12464700
references.citation: Physiol Rev. 2010 Apr;90(2):419-63
references.pmid: 20393190
references.citation: J Neurosci. 2003 Sep 24;23(25):8800-7
references.pmid: 14507980
references.citation: Brain Res. 2007 Jun 4;1152:139-57
references.pmid: 17442279
references.citation: Nat Neurosci. 2010 Apr;13(4):489-94
references.pmid: 20208529
references.citation: J Physiol. 2008 Mar 15;586(6):1503-8
references.pmid: 18202092
references.citation: Neuron. 2014 Jan 22;81(2):428-37
references.pmid: 24462103
references.citation: Learn Mem. 2007 Aug 01;14(8):520-4
references.pmid: 17671108
references.citation: Learn Mem. 2004 Sep-Oct;11(5):501-9
references.pmid: 15466300
references.citation: Biol Psychiatry. 2006 Aug 15;60(4):352-60
references.pmid: 16616731
references.citation: Nat Neurosci. 2012 Oct;15(10):1359-61
references.pmid: 22941108
references.citation: Neuron. 2007 Mar 15;53(6):871-80
references.pmid: 17359921
references.citation: Cereb Cortex. 2011 Mar;21(3):530-8
references.pmid: 20576926
references.citation: J Neurosci. 2004 Jun 23;24(25):5704-10
references.pmid: 15215292