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Recalling Safety: Cooperative Functions of the Ventromedial Prefrontal Cortex and the Hippocampus in Extinction

Published online by Cambridge University Press:  07 November 2014

Kevin A. Corcoran  and
Gregory J. Quirk
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Abstract

Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.

Type
Review Article
Information
CNS Spectrums , Volume 12 , Issue 3 , March 2007 , pp. 200 - 206
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

1.Blanchard, DC, Blanchard, RJ. Innate and conditioned reactions to threat in rats with amygdaloid lesions. J Comp Physiol Psychol. 1972;81:281–290.CrossRefGoogle ScholarPubMed
2.Repa, JC, Muller, J, Apergis, J, Desrochers, TM, Zhou, Y, LeDoux, JE. Two different lateral amygdala cell populations contribute to the initiation and storage of memory. Nat Neurosci. 2001;4:724–731.CrossRefGoogle Scholar
3.Fendt, M, Fanselow, MSThe neuroanatomical and neurochemical basis of conditioned fear. Neurosci Biobehav Rev. 1999;23:743–760.CrossRefGoogle ScholarPubMed
4.Gale, GD, Anagnostaras, SG, Godsil, BP, et al.Role of the basolateral amygdala in the storage of fear memories across the adult lifetime of rats. J Neurosci. 2004;24:3810–3815.CrossRefGoogle ScholarPubMed
5.Harris, JA, Jones, ML, Bailey, GK, Westbrook, RF. Contextual control over conditioned responding in an extinction paradigm. J Exp Psychol Anim Behav Process. 2000;26:174–185.CrossRefGoogle Scholar
6.Myers, KM, Davis, M. Behavioral and neural analysis of extinction. Neuron. 2002;36:567–584.CrossRefGoogle ScholarPubMed
7.Milad, MR, Rauch, SL, Pitman, RK, Quirk, GJ. Fear extinction in rats: Implications for human brain imaging and anxiety disorders. Biol Psychol. 2006;73:61–71.CrossRefGoogle ScholarPubMed
8.Bouton, ME, García-Gutiérrez, A, Zilski, J, Moody, EW. Extinction in multiple contexts does not necessarily make extinction less vulnerable to relapse. Behav Res Ther. 2006;44:983–994.CrossRefGoogle Scholar
9.Bouton, ME, Bolles, RC. Contextual control of the extinction of conditioned fear. Learn Motiv. 1979;10:445–466.CrossRefGoogle Scholar
10.Milad, MR, Orr, SP, Pitman, RK, Rauch, SL. Context modulation of memory for fear extinction in humans. Psychophysiology. 2005;42:456–464.CrossRefGoogle ScholarPubMed
11.Quirk, GJ. Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery. Learn Mem. 2002;9:402–407.CrossRefGoogle ScholarPubMed
12.Rescorla, RA. Spontaneous recovery. Learn Mem. 2004;11:501–509.CrossRefGoogle ScholarPubMed
13.Corcoran, KA, Maren, S. Hippocampal inactivation disrupts contextual retrieval of fear memory after extinction. J Neurosci. 2001;21:1720–1726.CrossRefGoogle ScholarPubMed
14.Bouton, ME. Context, time, and memory retrieval in the interference paradigms of Pavlovian learning. Psychol Bull. 1993;114:80–99.CrossRefGoogle ScholarPubMed
15.Rothbaum, BO, Davis, M. Applying learning principles to the treatment of posttrauma reactions. Ann N Y Acad Sci. 2003;1008:112–121.CrossRefGoogle Scholar
16.Charney, DS. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry. 2004;161:195–216.CrossRefGoogle ScholarPubMed
17.Davis, M. Neurobiology of fear responses: the role of the amygdala. J Neuropsychiatry Clin Neurosci. 1997;9:382–402.Google ScholarPubMed
18.Fanselow, MS, Gale, GD. The amygdala, fear, and memory. Ann N Y Acad Sci. 2003;985:125–134.CrossRefGoogle ScholarPubMed
19.Maren, S, Quirk, GJ. Neuronal signalling of fear memory. Nat Rev Neurosci. 2004;5:844–852.CrossRefGoogle ScholarPubMed
20.Lamprecht, R, LeDoux, J. Structural plasticity and memory. Nat Rev Neurosci. 2004;5:45–54.CrossRefGoogle ScholarPubMed
21.Phelps, EA. Emotion and cognition: insights from studies of the human amygdala. Annu Rev Psychol. 2006;57:27–53.CrossRefGoogle ScholarPubMed
22.Falls, WA, Miserendino, MJ, Davis, M. Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala. J Neurosci. 1992;12:854–863.CrossRefGoogle ScholarPubMed
23.Lu, KT, Walker, DL, Davis, M. Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle. J Neurosci. 2001;21:RC162.CrossRefGoogle ScholarPubMed
24.Lin, CH, Yeh, SH, Lu, HY, Gean, PW. The similarities and diversities of signal pathways leading to consolidation of conditioning and consolidation of extinction of fear memory. J Neurosci. 2003;23:8310–8317.CrossRefGoogle ScholarPubMed
25.Herry, C, Trifilieff, P, Micheau, J, Luthi, A, Mons, N. Extinction of auditory fear conditioning requires MAPK/ERK activation in the basolateral amygdala. Eur J Neurosci. 2006;24:261–269.CrossRefGoogle ScholarPubMed
26.Yang, YL, Lu, KT. Facilitation of conditioned fear extinction by d-cycloserine is mediated by mitogen-activated protein kinase and phoshpatidylinositol 3-kinase cascades and requires de novo protein synthesis in basolateral nucleus of amygdala. Neuroscience. 2005;134:247–260.CrossRefGoogle Scholar
27.Chhatwal, JP, Myers, KM, Ressler, KJ, Davis, M. Regulation of gephyrin and GABAA receptor binding within the amygdala after fear acquisition and extinction. J Neurosci. 2005;25:502–506.CrossRefGoogle ScholarPubMed
28.Harris, JA, Westbrook, RFEvidence that GABA transmission mediates context-specific extinction of learned fear. Psychopharmacology (Berl). 1998;140:105–115.CrossRefGoogle ScholarPubMed
29.Vertes, RP. Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse. 2004;51:32–58.CrossRefGoogle ScholarPubMed
30.McDonald, AJ, Mascagni, F, Guo, L. Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience. 1996;71:55–75.CrossRefGoogle Scholar
31.Pinto, AO, Sesack, SR. Prefrontal cortex projections to the rat amygdala: spatial relationships to dopamine and serotonin afferents. Ann N Y Acad Sci. 2003;985:542–544.Google Scholar
32.Royer, S, Martina, M, Pare, D. An inhibitory interface gates impulse traffic between the input and output stations of the amygdala. J Neurosci. 1999;19:10575–10583.CrossRefGoogle ScholarPubMed
33.Berretta, S, Pantazopoulos, H, Caldera, M, Pantazopoulos, P, Pare, D. Infralimbic cortex activation increases c-Fos expression in intercalated neurons of the amygdala. Neuroscience. 2005;132:943–953.CrossRefGoogle ScholarPubMed
34.Quirk, GJ, Likhtik, E, Pelletier, JG, Pare, D. Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. J Neurosci. 2003;23:8800–8807.CrossRefGoogle ScholarPubMed
35.Pare, D, Quirk, GJ, LeDoux, JE. New vistas on amygdala networks in conditioned fear. J Neurophysiol. 2004;92:1–9.CrossRefGoogle ScholarPubMed
36.Lebron, K, Milad, MR, Quirk, GJ. Delayed recall of fear extinction in rats with lesions of ventral medial prefrontal cortex. Learn Mem. 2004;11:544–548.CrossRefGoogle ScholarPubMed
37.Quirk, GJ, Russo, GK, Barron, JL, Lebron, K. The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J Neurosci. 2000;20:6225–6231.CrossRefGoogle ScholarPubMed
38.Burgos-Robles, A, Vidal-Gonzalez, I, Santini, E, Quirk, GJ. Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex. Neuron. In press.Google Scholar
39.Santini, E, Ge, H, Ren, K, Pena, DO, Quirk, GJ. Consolidation of fear extinction requires protein synthesis in the medial prefrontal cortex. J Neurosci. 2004;24:5704–5710.CrossRefGoogle ScholarPubMed
40.Lin, H, Su, C, Gean, P, Huang, A. Essential role for prefrontal cortex CB1 receptors in the extinction of fear memory. Society for Neuroscience Abstracts. 2006;373.1.Google Scholar
41.Zushida, K, Sakurai, M, Wada, K, Sekiguchi, M. Facilitation of extinction learning for contextual fear memory by PEPA: a potentiator of AMPA receptors. J Neurosci. 2007;27:158–166.CrossRefGoogle Scholar
42.Herry, C, Garcia, R. Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice. J Neurosci. 2002;22:577–583.CrossRefGoogle Scholar
43.Milad, MR, Quirk, GJ. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature. 2002;420:70–74.CrossRefGoogle ScholarPubMed
44.Maren, S, Aharonov, G, Fanselow, MS. Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats. Behav Brain Res. 1997;88:261–274.CrossRefGoogle ScholarPubMed
45.Anglada-Figueroa, D, Quirk, GJ. Lesions of the basal amygdala block expression of conditioned fear but not extinction. J Neurosci. 2005;25:9680–9685.CrossRefGoogle Scholar
46.Sierra-Mercado, D, Corcoran, KA, Lebron, K, Quirk, GJ. Inactivation of ventromedial prefrontal cortex reduces expression of conditioned fear and impairs subsequent recall of extinction. Eur J Neurosci. 2006;24:1751–1758.CrossRefGoogle ScholarPubMed
47.Corcoran, KA, Quirk, GJ. Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears. J Neurosci. 2007;27:840–844.CrossRefGoogle Scholar
48.Shah, AA, Sjovold, T, Treit, D. Inactivation of the medial prefrontal cortex with the GABAA receptor agonist muscimol increases open-arm activity in the elevated plus-maze and attenuates shock-probe burying in rats. Brain Res. 2004;1028:112–115.Google Scholar
49.Blum, S, Hebert, AE, Dash, PK. A role for the prefrontal cortex in recall of recent and remote memories. Neuroreport. 2006;17:341–344.CrossRefGoogle ScholarPubMed
50.Vidal-Gonzalez, I, Vidal-Gonzalez, B, Rauch, SL, Quirk, GJ. Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learn Mem. 2006;13:728–733.CrossRefGoogle ScholarPubMed
51.Poucet, B, Lenck-Santini, PP, Hok, V, et al.Spatial navigation and hippocampal place cell firing: the problem of goal encoding. Rev Neurosci. 2004;15:89–107.CrossRefGoogle ScholarPubMed
52.Corcoran, KA, Desmond, TJ, Frey, KA, Maren, S. Hippocampal inactivation disrupts the acquisition and contextual encoding of fear extinction. J Neurosci. 2005;25:8978–8987.CrossRefGoogle ScholarPubMed
53.Corcoran, KA, Maren, S. Factors regulating the effects of hippocampal inactivation on renewal of conditional fear after extinction. Learn Mem. 2004;11:598–603.CrossRefGoogle ScholarPubMed
54.Bouton, ME, Westbrook, RF, Corcoran, KA, Maren, S. Contextual and temporal modulation of extinction: behavioral and biological mechanisms. Biol Psychiatry. 2006;60:352–360.CrossRefGoogle ScholarPubMed
55.Frankland, PW, Bontempi, B, Talton, LE, Kaczmarek, L, Silva, AJ. The involvement of the anterior cingulate cortex in remote contextual fear memory. Science. 2004;304:881–883.CrossRefGoogle ScholarPubMed
56.Hobin, JA, Goosens, KA, Maren, S. Context-dependent neuronal activity in the lateral amygdala represents fear memories after extinction. J Neurosci. 2003;23:8410–8416.CrossRefGoogle ScholarPubMed
57.Sotres-Bayon, F, Bush, DE, LeDoux, JE. Emotional perseveration: an update on prefrontal-amygdala interactions in fear extinction. Learn Mem. 2004;11:525–535.CrossRefGoogle ScholarPubMed
58.Swanson, LW. A direct projection from Ammon's horn to prefrontal cortex in the rat. Brain Res. 1981;217:150–154.CrossRefGoogle ScholarPubMed
59.Conde, F, Maire-Lepoivre, E, Audinat, E, Crepel, F. Afferent connections of the medial frontal cortex of the rat. II. Cortical and subcortical afferents. J Comp Neurol. 1995;352:567–593.CrossRefGoogle ScholarPubMed
60.Tierney, PL, Degenetais, E, Thierry, AM, Glowinski, J, Gioanni, Y. Influence of the hippocampus on interneurons of the rat prefrontal cortex. Eur J Neurosci. 2004;20:514–524.CrossRefGoogle ScholarPubMed
61.Farinelli, M, Deschaux, O, Hugues, S, Thevenet, A, Garcia, R. Hippocampal train stimulation modulates recall of fear extinction independently of prefrontal cortex synaptic plasticity and lesions. Learn Mem. 2006;13:329–334.CrossRefGoogle ScholarPubMed
62.Siapas, AG, Lubenov, EV, Wilson, MA. Prefrontal phase locking to hippocampal theta oscillations. Neuron. 2005;46:141–151.CrossRefGoogle ScholarPubMed
63.Ishikawa, A, Nakamura, S. Convergence and interaction of hippocampal and amygdalar projections within the prefrontal cortex in the rat. J Neurosci. 2003;23:9987–9995.CrossRefGoogle ScholarPubMed
64.Phelps, EA, Delgado, MR, Nearing, KI, LeDoux, JE. Extinction learning in humans: role of the amygdala and vmPFC. Neuron. 2004;43:897–905.CrossRefGoogle ScholarPubMed
65.Milad, MR, Wright, Cl, Orr, SP, Pitman, RK, Quirk, GJ, Rauch, SL. Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol Psychol. In press.Google Scholar
66.Kalisch, R, Korenfeld, E, Stefan, KE, Seymour, B, Dolan, RJ. Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network. J Neurosci. 2006;26:9503–9511.CrossRefGoogle ScholarPubMed
67.Rauch, SL, Shin, LM, Segal, E. Selectively reduced regional cortical volumes in posttraumatic stress disorder. Neuroreport. 2003;14:913–916.Google Scholar
68.Gilbertson, MW, Shenton, ME, Ciszewski, A. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci. 2002;5:1242–1247.CrossRefGoogle ScholarPubMed
69.Britton, JC, Phan, KL, Taylor, SF, Fig, LM, Liberzon, I. Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery. Biol Psychiatry. 2005;57:832–840.CrossRefGoogle ScholarPubMed
70.Shin, LM, Orr, SP, Carson, MA, et al.Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Arch Gen Psychiatry. 2004;61:168–176.CrossRefGoogle ScholarPubMed
71.Ochsner, KN, Gross, JJ. The cognitive control of emotion. Trends Cogn Sci. 2005;9:242–249.CrossRefGoogle ScholarPubMed
72.Urry, HL, van Reekum, CM, Johnstone, T. Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults. J Neurosci. 2006;26:4415–4425.CrossRefGoogle ScholarPubMed
73.Gonzalez-Lima, F, Bruchey, AK. Extinction memory improvement by the metabolic enhancer methylene blue. Learn Mem. 2004;11:633–640.CrossRefGoogle ScholarPubMed
74.Ressler, KJ, Rothbaum, BO, Tannenbaum, L, et al.Cognitive enhancers as adjuncts to psychotherapy: Use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry. 2004;61:1136–1144.CrossRefGoogle ScholarPubMed
75.Hofmann, SG, Meuret, AE, Smits, JA, et al.Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. Arch Gen Psychiatry. 2006;63:298–304.CrossRefGoogle ScholarPubMed
76.Quirk, GJ, Garcia, R, Gonzalez-Lima, F. Prefrontal mechanisms in extinction of conditioned fear. Biol Psychiatry. 2006;60:337–343.CrossRefGoogle ScholarPubMed