NM  Vol.2 No.3 , September 2011
Brain Interactions between Extinction and Reconsolidation in the Treatment of Fear Memories
ABSTRACT
Memory traces become labile at the time of retrieval, and this initiates two protein synthesis-dependent processes in the brain: extinction, which inhibits their further retrieval, and reconsolidation, which may enhance retrieval or change the memory’s content. Extinction may itself suffer reconsolidation. Interactions between these processes may be applied to the treatment of fear memories, such as those underlying the post-traumatic stress disorder.

Cite this paper
nullD. Sartor, N. Fiorenza, J. Myskiw and I. Izquierdo, "Brain Interactions between Extinction and Reconsolidation in the Treatment of Fear Memories," Neuroscience and Medicine, Vol. 2 No. 3, 2011, pp. 232-238. doi: 10.4236/nm.2011.23032.
References
[1]   I. Izquierdo, “Memoria,” 2nd Edition, Porto Alegre, Art- Med, 2011.

[2]   I. P. Pavlov, “Conditioned Reflexes,” Dover, New York, 1956.

[3]   S. J. Sara, “Strengthening the Shaky Trace through Retrieval,” Nature Review Neuroscience, Vol. 1, No. 3, 2000, pp. 212-213. doi:10.1038/35044575

[4]   G. J. Quirk, D. Paré, R. Richardson, C. Herry, M. H. Monfils, D. Schiller and A. Vicentic, “Erasing fear Me- mories with Extinction Training,” The Journal of Neuro- science, Vol. 30, No. 45, 2010, pp. 14993-14997. doi:10.1523/JNEUROSCI.4268-10.2010

[5]   I. Izquierdo, L. R. Bevilaqua, R. H. Lima, J. H. Clarke and M. Cammarota, “Extinction Learning: Neurological Features, Therapeutic Applications, and Effect of Aging,” Future Neurology, Vol. 3, 2008, pp. 133-141. doi:10.2217/14796708.3.2.133

[6]   L. M. Bevilaqua, M. Cammarota, J. H. Medina, I. Izquierdo, “Extinction” In: L. Sher and A. Vilens, Eds., Neurobiol- ogy of Posttraumatic Stress Disorder, Nova Publishers, New York, 2010, pp. 309-330.

[7]   M. Cammarota, L. R. Bevilaqua, D. M. Barros, M. R. M. Vianna, L. A. Izquierdo and J. H. Medina, “Retrieval and the Extinction of Memory,” Cellular and Molecular Neurobiology, Vol. 256, 2002, pp. 465-474.

[8]   L. M. Perez-Cuesta, Y. Hepp, M. E. Pedreira and H. Maldonado, “Extinction Memory in the Crab Chasmag- nathus: Recovery Protocols and Effects of Multi-Trial Extinction Training,” Learning and Memory, Vol. 14, No. 1, 2007, pp. 101-108. doi:10.1101/lm.413507

[9]   W. S. Beckett, “Post-Traumatic Stress Disorder,” The New England Journal of Medicine, Vol. 346, No. 2, 2002. pp. 130-132. doi:10.1056/NEJM200201103460213

[10]   C. Forcato, M. L. Rodríguez, M. E. Pedreira and H. Maldonado, “Reconsolidation in Humans Opens up De- clarative Memory to the Entrance of New Information,” Neurobiology of Learning and Memory, Vol. 93, No. 1, 2010, pp. 77-84.

[11]   M. Cammarota, L. R. Bevilaqua, J. I. Rossato, M. R. Ramírez, J. H. Medina and I. Izquierdo, “Relationship between Short- and Long-Term Memory and Short- and Long-Term Extinction,” Neurobiology of Learning and Memory, Vol. 84, No. 1, 2005, pp. 25-32. doi:10.1016/j.nlm.2005.03.002

[12]   I. Izquierdo, “Endogenous State Dependency: Memory Depends on the Relation between the Neurohumoral and Hormonal States Present after Training and at the Time of Testing,” In: G. Lynch, J. L. McGaugh and N. M. Weinberger, Eds., Neurobiology of Learning and Memory, Guilford Press, New York, 1984, pp. 333-350.

[13]   L. M. Igaz, M. R. Vianna, J. H. Medina and I. Izquierdo, “Two Time Periods of Hippocampal Rna Synthesis Are Required for Memory Consolidation of Fear-Motivated Learning,” Journal of Neuroscience, Vol. 22, No. 3, 2002, pp. 6781-6789.

[14]   R. A. Rescorla, “Spontaneous Recovery,” Learning and Memory, Vol. 11, 2004, pp. 501-509. doi:10.1101/lm.77504

[15]   K. Nader, G. E. Schafe and J. E. LeDoux, “Fear Memo- ries Require Protein Synthesis in the Amygdala for Re- consolidation after Retrieval,” Nature, Vol. 416, 2000, pp. 722-726.

[16]   J. I. Rossato, L. R. Bevilaqua, J. H. Medina, I. Izquierdo and M. Cammarota, “Retrieval Induces Hippocampus- Dependent Reconsolidation of Spatial Memory,” Learn- ing and Memory, Vol. 13, 2006, pp. 431-441. doi:10.1101/lm.315206

[17]   J. I. Rossato, L. R. Bevilaqua, I. Izquierdo, J. H. Medina and M. Cammarota, “Retrieval Induces Reconsolidation of Fear Extinction Memory,” Proceeding of the National Academy of Science of the United States of America, Vol. 107, No. 50, 2010, pp. 21801-21805.

[18]   M. R. M. Vianna, G. Szapiro, J. L. McGaugh, J. H. Medina and I. Izquierdo, “Retrieval of Memory for Fear- Motivated Training Initiates Extinction Requiring Protein Synthesis in the Rat Hippocampus,” Proceeding of the National Academy of Science of the United States of America, Vol. 98, No. 21, 2001, pp. 12251-12254.

[19]   G. Szapiro, L. A. Izquierdo, M. Alonso, D. M. Barros, G. Paratcha, P.G. Ardenghi, P. Pereira, J. H. Medina and I. Izquierdo, “Participation of Hippocampal Metabotropic Glutamate Receptors, Protein Kinase A and Mitogen– Activated Protein Kinases in Memory Retrieval,” Neuro- science, Vol. 99, No. 1, 2000, pp. 1-5.

[20]   G. Szapiro, M. R. M. Vianna, J. L. McGaugh, J. H. Me- dina and I. Izquierdo, “The Role of NMDA Glutamate Receptors, PKA, MAPK and CAMKII in the Hippocam- pus in the Extinction of Conditioned Fear,” Hippocampus, Vol. 13, 2003, pp. 53-58.

[21]   M. H. Monfils, K. K. Cowansage, E. Klann and J. E. Le- Doux, “Extinction-Reconsolidation Boundaries: Key to Persistent Attenuation of Fear Memories,” Science, Vol. 324, No. 5929, 2009, pp. 951-955.

[22]   M. H. Milekic and C. M. Alberini, “Temporally Graded Requirement for Protein Synthesis Following Memory Reactivation,” Neuron, Vol. 36, No. 3, 2002, pp. 531-535.

[23]   I. Izquierdo, W. Wyrwicka, G. Sierra and J. P. Segundo, “Etablissement de Reflexes Conditionnés de Trace Pen- dant le Sommeil Naturel Chez le Chat. Actual,” Neuro- physiology, Vol. 6, 1965, pp. 277-296.

[24]   P. Janet, “The Major Symptoms of Hysteria,” Macmillan, New York, 1906.

[25]   J. C. Nemiah, “Comprehensive Textbook of Psychiatry,” In: H. I. Kaplan and B. J. Sadock, Eds., Williams and Wilkins, Baltimore, 1985, pp. 894-942.

[26]   J. L. McGaugh, “A Century of Consolidation,” Science, Vol. 287, No. 5451, 2000, pp. 248-351.

[27]   S. P. Orr, M. R. Milad, L. J. Metzger, N. B. Lasko, M. W. Gilbertson and R. K. Pitman, “Effects of β-Receptor Blockade, PTSD Diagnosis, and Explicit Threat on the Extinction and Retention of an Aversively Conditioned Response,” Biological Psychology, Vol. 73, No. 3, 2006, pp. 262-271. doi:10.1016/j.biopsycho.2006.05.001

[28]   M. J. Herz, C. E. Spooner and A. A. Cherkin, “EEG and Multiple Unit Responses to the Amnes Sic Agent Flu- rothyl in Chicks,” Proceedings of the Western Pharma- cology Society, Vol. 12, 1969, pp. 62-64.

[29]   M. T. Alkire, R. Gruver, J. Miller, J. R. McReynolds, E. L. Hahn and L. Cahill, “Neuroimaging Analysis of an Anesthetic Gas that Blocks Human Emotional Memory,” Proceeding of the National Academy of Science of the United States of America, Vol. 115, 2008, pp. 1722- 1727.

[30]   D. J. de Quervain, D. Bentz, T. Michael, O. C. Bolt, B. K. Wiederhold, J. Margraf and F. H. Wilhelm, “Glucocorti- coids Enhance Extinction-Based Psychotherapy,” Proceeding of the National Academy of Science of the United States of America, Vol. 108, No. 16, 2011, pp. 6621- 6625.

[31]   D. J. de Quervain, “Glucocorticoid-Induced Inhibition of Memory Retrieval: Implications for Posttraumatic Stress Disorder,” Annals of the New York Academy of Science, Vol. 1071, 2006, pp. 216-220. doi:10.1196/annals.1364.016

[32]   A. Aerni, R. Traber, C. Hock, B. Roozendaal, G. Schel- ling, A. Papassotiropoulos, R. M. Nitsch, U. Schnyder and D. de Quervain, “Low-Dose Cortisol for Symptoms of Posttraumatic Stress Disorder,” The American Journal of Psychiatry, Vol. 161, No. 8, 2004, pp. 1488-1490. doi:10.1176/appi.ajp.161.8.1488

[33]   D. J. de Quervain, K. Henke, A. Aerni, V. Treyer, J. L. McGaugh, T. Berthold, R. M. Nitsch, A. Buck, B. Rooz- endaal and C. Hock, “Glucocorticoid-Induced Impairment of Declarative Memory Retrieval is Associated with Re- duced Blood Flow in the Medial Temporal Lobe,” The European Journal of Neuroscience, Vol. 17, No. 6, 2003, pp. 1296-1302. doi:10.1046/j.1460-9568.2003.02542.x

[34]   M. Davis, K. M. Myers, J. Chhatwal and K. J. Ressler, “Pharmacological Treatments that Facilitate Extinction of Fear: Relevance to Psychotherapy,” The Journal of the American Society for Experimental NeuroTherapeutics, Vol. 3, No. 1, 2006, pp. 82-96.

[35]   D. M. Barros, L. A. Izquierdo, T. Mello e Souza, P. Ar- denghi, P. Pereira, J. H. Medina and I. Izquierdo, “Mo- lecular Signaling Pathways in the Cerebral Cortex Are Required for Retrieval of One-Trial Avoidance Learning in Rats,” Behavioural Brain Research, Vol. 114, No. 200, pp. 183-192.

[36]   D. M. Barros, T. Mello e Souza, T. De David, H. Choi, A. Aguzzoli, C. Madche, P. Ardenghi, J. H. Medina and I. Izquierdo, “Simultaneous Modulation of Retrieval by Dopaminergic D(1), Beta-Noradrenergic, Serotonergic- 1A and Cholinergic Muscarinic Receptors in Cortical Structures of the Rat,” Behavioural Brain Research, Vol. 124, 2001, pp. 1-7. doi:10.1016/S0166-4328(01)00208-X

[37]   D. Schiller, M. H. Monfils, C. M. Raio, D. C. Johnson, J. E. LeDoux and E. A. Phelps, “Preventing the Return of Fear in Humans Using Reconsolidation Update Mecha- nisms,” Nature, Vol. 463, No. 7277, 2010, pp. 49-53.

[38]   P. Garcia de la Torre, C. J. Rodríguez-Ortiz, I. Balderas and F. Bermúdez-Rattoni, “Differential Participation of Temporal Structures in the Consolidation and Reconsoli- dation of Taste Aversion Extinction,” The European Journal of Neuroscience, Vol. 32, No. 6, 2010, pp. 1018- 1023.

[39]   R. H. Lima, J. I. Rossato, C. R. Furini, L. R. Bevilaqua, I. Izquierdo and M. Cammarota, “Infusion of Protein Syn- thesis Inhibitors in the Entorhinal Cortex Blocks Con- solidation but Not Reconsolidation of Object Recognition Memory,” Neurobiology of Learning and Memory, Vol. 91, No. 4, 2009, pp. 466-472. doi:10.1016/j.nlm.2008.12.009

[40]   J. C. Myskiw, N. G. Fiorenza, L. A. Izquierdo and I. Izquierdo, “Molecular Mechanisms in Hippocampus and Basolateral Amygdala but Not in Parietal or Cingulate Cortex Are Involved in Extinction of One-Trial Avoid- ance Learning,” Neurobiology of Learning and Memory, Vol. 94, No. 2, 2010, pp. 285-291. doi:10.1016/j.nlm.2010.06.007

[41]   L. R. Bevilaqua, J. S. Bonini, J. I. Rossatto, L. A. Izquierdo, M. Cammarota and I. Izquierdo, “The En- torhinal Cortex Plays a Role in Extinction,” Neurobiology of Learning and Memory, Vol. 85, No. 2, 2006, pp. 192- 197. doi:10.1016/j.nlm.2005.10.001

[42]   M. R. Milad and G. J. Quirk, “Neurons in Medial Pre- frontal Cortex Signal Memory for Fear Extinction,” Na- ture, Vol. 420, No. 6911, 2002, pp. 7-74.

[43]   E. Santini, H. Ge, K. Ren, S. Pe?a de Ortiz and G. J. Quirk, “Consolidation of Fear Extinction Requires Pro- tein Synthesis in the Medial Prefrontal Cortex,” Journal of Neuroscience, Vol. 24, No. 25, 2004, pp. 5704-5710. doi:10.1523/JNEUROSCI.0786-04.2004

[44]   M. R. Delgado, K. I. Nearing, J. E. Ledoux and E. A. Phelps, “Neural Circuitry Underlying the Regulation of Conditioned Fear and Its Relation to Extinction,” Neuron, Vol. 59, No. 5, 2008, pp. 829-838.

[45]   E. Likhtik, D. Popa, J. Apergis-Schoute, G. A. Fidacaro and D. Paré, “Amygdala Intercalated Neurons Are Re- quired for Expression of Fear Extinction,” Nature, Vol. 454, No. 7204, 2008, pp. 642-645.

[46]   M. R. Milad, C. I. Wright, S. P. Orr, R. K. Pitman, G. J. Quirk and S. L. Rauch, “Recall of Fear Extinction in Humans Activates the Ventromedial Prefrontal Cortex And Hippocampus in Concert,” Biological Psychology, Vol. 62, No. 5, 2007, pp. 446-454. doi:10.1016/j.biopsych.2006.10.011

[47]   M. R. Milad, B. T. Quinn, R. K. Pitman, S. P. Orr, B. Fischl and S. L. Rauch, “Thickness of Ventromedial Pre- frontal Cortex in Humans Is Correlated with Extinction Memory,” Proceeding of the National Academy of Science of the United States of America, Vol. 102, No. 30, 2005, pp. 10706-10711.

[48]   R. K. Pitman and D. L. Delahanty, “Conceptually Driven Pharmacologic Approaches to Acute Trauma,” CNS Spec- trums, Vol. 10, No. 2, 2005, pp. 99-106.

[49]   R. K. Pitman, K. M. Sanders, R. M. Zusman, A. R. Healy, F. Cheema, N. B. Lasko, L. Cahill and S. P. Orr, “Pilot study of Secondary Prevention of Posttraumatic Stress Disorder with Propranolol,” Biology Psychiatry, Vol. 51, No. 2, 2002, pp. 189-51192. doi:10.1016/S0006-3223(01)01279-3

[50]   B. D. Heifets and P. E. Castillo, “Endocannabinoid Sig- naling and Long-Term Synaptic Plasticity,” Annual Re- view of Physiology, Vol. 71, 2009, pp. 283-306. doi:10.1146/annurev.physiol.010908.163149

[51]   G. Marsicano and B. Lutz, “Neuromodulatory Functions of the Endocannabinoid System,” Journal of Endocri- nological Investigation, Vol. 29, No. 3 Suppl, 2006, pp. 27-46.

[52]   M. R. Milad, M. A. Zeidan, A. Contero, R. K. Pitman, A. Klibanski, S. L. Rauch and J. M. Goldstein, “The Influ- ence of Gonadal Hormones on Conditioned Fear Extinc- tion in Healthy Humans,” Neuroscience, Vol. 168, No. 3, 2010, pp. 653-658.

[53]   K. J. Ressler, B. O. Rothbaum, L. Tannenbaum, P. Anderson, K. Graap, E. Zimand, L. Hodges and M. Davis, “Cognitive Enhancers as Adjuncts to Psychotherapy: Use of D-Cycloserine in Phobic Individuals to Facilitate Ex- tinction of Fear,” Archives of General Psychiatry, Vol. 61, No. 11, 2004, pp. 1136-1144. doi:10.1001/archpsyc.61.11.1136

[54]   M. Davis, K. Ressler, B. O. Rothbaum and R. Richardson, “Effects of D-Cycloserine on Extinction: Translation from Preclinical to Clinical Work,” Biological Psychiatry, Vol. 60, No. 4, 2006, pp. 369-375. doi:10.1016/j.biopsych.2006.03.084

 
 
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