QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 27, 2006, 26(39):10051-10056; doi:10.1523/JNEUROSCI.2466-06.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (39) Citing Articles via Google Scholar Google Scholar Articles by Lee, J. L. C. Articles by Everitt, B. J. Search for Related Content PubMed PubMed Citation Articles by Lee, J. L. C. Articles by Everitt, B. J.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Reconsolidation and Extinction of Conditioned Fear: Inhibition and Potentiation

Jonathan L. C. Lee, Amy L. Milton, and Barry J. Everitt

Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom

Correspondence should be addressed to Jonathan L. C. Lee, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Email: jlcl2{at}cam.ac.uk

NMDA receptors are important for the acquisition, reconsolidation, and extinction of memories. NMDA receptor antagonists impair these memory processes, whereas the partial agonist D-cycloserine (DCS) potentiates both learning and extinction. Here, we used DCS and the noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) to investigate the effects of enhancing and blocking NMDA receptor-mediated glutamatergic transmission on the reconsolidation and extinction of a conditioned fear memory. Either long extinction training or short memory reactivation sessions were used to preferentially engage extinction and reconsolidation processes, respectively. MK-801 blocked extinction to maintain high levels of conditioned freezing, and DCS potentiated extinction to reduce freezing, when they were administered before a long extinction training session. However, the opposite behavioral outcome was observed when the brief memory reactivation session was used: MK-801 administration impaired, whereas DCS increased, freezing, likely reflecting impairment and enhancement of reconsolidation, respectively. Finally, by using localized intracerebral infusions, we showed that the basolateral amygdala is a primary locus of action of systemically administered DCS. Thus, intrabasolateral amygdala DCS potentiated both the extinction and the reconsolidation of fear conditioning, depending on the length of the extinction/memory reactivation session. Therefore, memory reconsolidation can be both disrupted and enhanced, and extinction can be both potentiated and impaired, either to reduce or increase conditioned fear. These results have important implications for the use of reconsolidation blockade and potentiation of extinction as treatment strategies for maladaptive memory disorders.

Key words: memory; reconsolidation; extinction; NMDA receptor; basolateral amygdala; rat

---

Received April 25, 2006; revised July 31, 2006; accepted Aug. 28, 2006.

Correspondence should be addressed to Jonathan L. C. Lee, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Email: jlcl2{at}cam.ac.uk

This article has been cited by other articles:

				B. D. Winters, M. C. Tucci, and M. DaCosta-Furtado Older and stronger object memories are selectively destabilized by reactivation in the presence of new information Learn. Mem., August 27, 2009; 16(9): 545 - 553. [Abstract] [Full Text] [PDF]

				M.-H. Monfils, K. K. Cowansage, E. Klann, and J. E. LeDoux Extinction-Reconsolidation Boundaries: Key to Persistent Attenuation of Fear Memories Science, May 15, 2009; 324(5929): 951 - 955. [Abstract] [Full Text] [PDF]

				G. P. Urcelay, D. S. Wheeler, and R. R. Miller Spacing extinction trials alleviates renewal and spontaneous recovery Learn Behav, February 1, 2009; 37(1): 60 - 73. [Abstract] [PDF]

				N. Mamiya, H. Fukushima, A. Suzuki, Z. Matsuyama, S. Homma, P. W. Frankland, and S. Kida Brain Region-Specific Gene Expression Activation Required for Reconsolidation and Extinction of Contextual Fear Memory J. Neurosci., January 14, 2009; 29(2): 402 - 413. [Abstract] [Full Text] [PDF]

				J. L.C. Lee, R. J. Gardner, V. J. Butler, and B. J. Everitt D-cycloserine potentiates the reconsolidation of cocaine-associated memories Learn. Mem., January 7, 2009; 16(1): 82 - 85. [Abstract] [Full Text] [PDF]

				R. Kalisch, B. Holt, P. Petrovic, B. De Martino, S. Kloppel, C. Buchel, and R. J. Dolan The NMDA Agonist D-Cycloserine Facilitates Fear Memory Consolidation in Humans Cereb Cortex, January 1, 2009; 19(1): 187 - 196. [Abstract] [Full Text] [PDF]

				T. E. Brown, B. R. Lee, and B. A. Sorg The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats Learn. Mem., December 2, 2008; 15(12): 857 - 865. [Abstract] [Full Text] [PDF]

				A. L. Milton, J. L. C. Lee, V. J. Butler, R. Gardner, and B. J. Everitt Intra-Amygdala and Systemic Antagonism of NMDA Receptors Prevents the Reconsolidation of Drug-Associated Memory and Impairs Subsequently Both Novel and Previously Acquired Drug-Seeking Behaviors J. Neurosci., August 13, 2008; 28(33): 8230 - 8237. [Abstract] [Full Text] [PDF]

				J. L.C. Lee and B. J. Everitt Reactivation-dependent amnesia in Pavlovian approach and instrumental transfer Learn. Mem., August 6, 2008; 15(8): 597 - 602. [Abstract] [Full Text] [PDF]

				J. L.C. Lee and B. J. Everitt Reactivation-dependent amnesia for appetitive memories is determined by the contingency of stimulus presentation Learn. Mem., May 28, 2008; 15(6): 390 - 393. [Abstract] [Full Text] [PDF]

				Y. H. Huang, Y. Lin, T. E. Brown, M.-H. Han, D. B. Saal, R. L. Neve, R. S. Zukin, B. A. Sorg, E. J. Nestler, R. C. Malenka, et al. CREB Modulates the Functional Output of Nucleus Accumbens Neurons: A CRITICAL ROLE OF N-METHYL-D-ASPARTATE GLUTAMATE RECEPTOR (NMDAR) RECEPTORS J. Biol. Chem., February 1, 2008; 283(5): 2751 - 2760. [Abstract] [Full Text] [PDF]

				T. W. Bredy and M. Barad The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear Learn. Mem., January 3, 2008; 15(1): 39 - 45. [Abstract] [Full Text] [PDF]

				M. H. Milekic, G. Pollonini, and C. M. Alberini Temporal requirement of C/EBP{beta} in the amygdala following reactivation but not acquisition of inhibitory avoidance Learn. Mem., July 18, 2007; 14(7): 504 - 511. [Abstract] [Full Text] [PDF]

				A. Gabriele and M. G. Packard D-Cycloserine enhances memory consolidation of hippocampus-dependent latent extinction Learn. Mem., July 1, 2007; 14(7): 468 - 471. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help