The Central Amygdala Nucleus via Corticotropin-Releasing Factor Is Necessary for Time-Limited Consolidation Processing but Not Storage of Contextual Fear Memory

Neurobiol Learn Mem. 2011 Jan;95(1):86-91. doi: 10.1016/j.nlm.2010.11.006. Epub 2010 Nov 17.


The central nucleus of the amygdala (CeA) is traditionally portrayed in fear conditioning as the key neural output that relays conditioned information established in the basolateral amygdala complex to extra-amygdalar brain structures that generate emotional responses. However, several recent studies have questioned this serial processing view of the amygdalar fear conditioning circuit by showing an influence of the CeA on memory consolidation. We previously reported that inhibition of endogenous CeA secretion of corticotropin-releasing factor (CRF) at the time of contextual training effectively impaired fear memory consolidation. However, the time-dependent range of CeA CRF secretion in facilitating consolidation processing has not been examined. Therefore, to address this issue, we performed CeA site-specific microinjections of CRF antisense oligonucleotides (CRF ASO) at several post-training time intervals. Rats microinjected with CRF ASO at post-training intervals up to 24-h subsequently exhibited significant impairments in contextual freezing retention in contrast to animals treated 96-h after training. To further establish the validity of the results, CeA fiber-sparing lesions were made at two distinct post-training periods (24-h and 96-h), corresponding respectively to the temporal intervals when CeA CRF ASO administration disrupted or had no significant effects on memory consolidation. Similar to the CeA CRF ASO results, CeA lesions made 24-h, but not 96-h, after training induced significant freezing deficits in the retention test. In conclusion, the current results demonstrate: (1) an extended involvement of CeA CRF in contextual memory consolidation and (2) that contextual fear memory storage is not dependent on a functional CeA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiology*
  • Animals
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / metabolism*
  • Electroshock
  • Fear / drug effects
  • Fear / physiology*
  • Freezing Reaction, Cataleptic / drug effects
  • Freezing Reaction, Cataleptic / physiology
  • Immunohistochemistry
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Microinjections
  • Oligodeoxyribonucleotides, Antisense / administration & dosage
  • Rats
  • Rats, Long-Evans


  • Oligodeoxyribonucleotides, Antisense
  • Corticotropin-Releasing Hormone