Resistance to extinction is associated with impaired immediate early gene induction in medial prefrontal cortex and amygdala.
Extinction of classical fear conditioning is thought to involve activity-dependent potentiation of synaptic transmission in the medial prefrontal cortex (mPFC), resulting in the inhibition of amygdala-dependent fear responses. While many studies have addressed the mechanisms underlying extinction learning, it is unclear what determines whether extinction memory is consolidated or whether spontaneous recovery of the fear response occurs. Here we show, using a combined electrophysiological and immunocytochemical approach, that spontaneous recovery of conditioned fear in mice is associated with a prolonged expression of long-term depression of synaptic transmission in the mPFC and the failure of induction of the immediate-early genesc-Fos and zif268 in the mPFC and the basolateral nucleus of the amygdala. This suggests that coordinated activity-dependent changes in gene expression in the mPFC and the amygdala may underlie the formation of long-term fear extinction memory.
Herry
Cyril
C
Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux I, Avenue des Facultés, 33405 Talence, France. cyril.herry@fmi.ch
Mons
Nicole
N
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count; D003214:Conditioning, Classical / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004594:Electrophysiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D017397:Prefrontal Cortex / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors