Counteracting molecular pathways regulating the reduction of fear: Implications for the treatment of anxiety diseases

Post-Traumatic Stress Disorder: Basic Science and Clinical Practice

Volumn , Issue , 2009, Pages 79-103

  Fischer, Andre ^a   Tsai, Li Huei ^b  

^a EUROPEAN NEUROSCIENCE INSTITUTE   (Germany)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Anxiety diseases; Cdk5; cycline dependent kinase 5; cytoskeleton; extinction; fear conditioning; hippocampus; MAP kinases; reduction of learned fear

Indexed keywords

EID: 84891883189     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-60327-329-9_4     Document Type: Chapter

References (119)

1. Deacon, B. J., and Abramowitz, J. S. (2004) Cognitive and behavioral treatments for anxiety disorders: a review of meta-analytic findings. J Clin Psychol 60, 429-41.
2. Ressler, K. J., Rothbaum, B. O., Tannenbaum, L., et al. (2004) Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear Arch Gen Psychiatry 61, 1136-44.
3. Adshead, G. (2000) Psychological therapies for post-traumatic stress disorder. Br J Psychiatry 177, 144-48.
4. Bisson, J., and Andrew, M. (2007) Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev 18, CD003388.
5. Ballenger, J. C. (1999) Current treatments of the anxiety disorders in adults. Biol Psychiatry 46, 1579-94.
6. Schoenfeld, F. B., Marmar, C. R., and Neylan, T. C. (2004) Current concepts in pharmacotherapy for posttraumatic stress disorder. Psychiatr Serv 55, 19-31.
7. Keane, T. M., Marshall, A. D., and Taft, C. T. (2006) Posttraumatic stress disorder: etiology, epidemiology, and treatment outcome. Annu Rev Clin Psychol 2, 161-97.
8. Kandel, E. R. (2001) The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030-38.
9. Davis, M., Falls W. A., Campeau, S., and Kim, M. (1993) Fear-potentiated startle: a neural and pharmacological analysis. Behav Brain Res 58, 175-98.
10. Tronson, N. C., Schrick, C., Fischer, A., et al. (2008) Regulatory mechanisms of fear extinction and depression-like behavior. Neuropsychopharmacology 33, 1570-83.
11. Siegmund, A., and Wotjak, C. T. (2007) A mouse model of posttraumatic stress disorder that distinguishes between conditioned and sensitised fear. J Psychiatr Res 41, 848-60.
12. Myers, K. M., and Davis, M. (2007) Mechanisms of fear extinction. Mol Psychiatry 12, 120-50.
13. Falls, W. A., Miserendino, M. J., and Davis, M. (1992) Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala. J Neurosci 12, 854-63.
14. Baker, J. D., and Azorlosa, J. L. (1996) The NMDA antagonist MK-801 blocks the extinction of Pavlovian fear conditioning. Behav Neurosci 10, 618-20.
15. Szapiro, G., Vianna, M. R., McGaugh, J. L., Medina, J. H., and I., I (2003) The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear. Hippocampus 13, 53-58.
16. Walker, D. L., Ressler, K. J., Lu, K. T., and Davis, M. (2002) Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats. J Neurosci 22, 2343.
17. Davis, M., Ressler, K., Rothbaum, B. O., and Richardson, R. (2006) Effects of D-cycloserine on extinction: translation from preclinical to clinical work. Biol Psychiatry 60, 369-75.
18. Guastella, A. J., Dadds, M. R., Lovibond, P. F., Mitchell, P., and Richardson, R. (2007) A randomized controlled trial of the effect of D-cycloserine on exposure therapy for spider fear. J Psychiatr Res 41, 466-71.
19. Pavlov, I. P. (1927) Conditioned Reflexes. New York : Oxford University Press.
20. Bouton, M. E. (2004) Context and behavioral processes in extinction. Learn Mem 11, 485-95.
21. Delamater, A. R. (2004) Experimental extinction in Pavlovian conditioning: behavioural and neuroscience perspectives. Q J Exp Psychol B 57, 97-132.
22. Rescorla, R. A. (2001) Experimental extinction in Pavlovian conditioning: behavioural neuroscience perspective. Q J Exp Psychol B 57, 97-132.
23. Lattal, K. M., Radulovic, J., and Lukowiak, K. (2006) Extinction: does it or doesn't it? The requirement of altered gene activity and new protein synthesis. Biol Psychiatry 60, 344-51.
24. Bouton, M. E. (1993) Context, time, and memory retrieval in the interference paradigms of Pavlovian learning. Psychol Bull 114, 80-99.
25. Konorski, J. (1946) Conditioned Reflexes and Neuronal Organisation. London : Cambridge University Press.
26. Wagner, A.R. (1981) SPO: a model of automatic memory processing in animal behavior. In: Spear, N. E., M. R. R., eds., Information Processing in Animals: Memory Mechanisms.
27. Kamprath, K., and Wotjak, C. T. (2004) Nonassociative learning processes determine expression and extinction of conditioned fear in mice. Learn Mem 11, 770-86.
28. McSweeney, F. K., and Swindell, S. (2002) Common processes may contribute to extinction and habituation. J Gen Psychol 129, 364-400.
29. Thomas, E., and Yadin, E. (1980) Multiple-unit activity in the septum during Pavlovian aversive conditioning: evidence for an inhibitory role of the septum. Exp Neurol 69, 50-60.
30. Waddell, J., Morris, R. W., and Bouton, M. E. (2006) Effects of bed nucleus of the stria terminalis lesions on conditioned anxiety: aversive conditioning with long-duration conditional stimuli and reinstatement of extinguished fear. Behav Neurosci 120, 324-36.
31. Rogan, M. T., Leon, K. S., Perez, D. L., and Kandel, E. R. (2005) Distinct neural signatures for safety and danger in the amygdala and striatum of the mouse. Neuron 46, 309-20.
32. Sotres-Bayon, F., Cain, C. K., and LeDoux, J. E. (2006) Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex. Biol Psychiatry 60, 329-36.
33. Barad, M., Gean, P. W., and Lutz, B. (2006) The role of the amygdala in the extinction of conditioned fear. Biol Psychiatry 15, 322-28.
34. Quirk, G. J., and Mueller, D. (2008) Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 33, 56-72.
35. Ji, J., and Maren, S. (2007) Hippocampal involvement in contextual modulation of fear extinction. Hippocampus 17, 749-58.
36. Fanselow, M. S., and LeDoux, J. E. (1999) Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron 23, 229-32.
37. Sanders, M. J., Wiltgen, B. J., and Fanselow, M. S. (2003) The place of the hippocampus in fear conditioning. Eur J Pharmacol 463, 217-23.
38. Hugues, S., and Garcia, R. (2007) Reorganization of learning-associated prefrontal synaptic plasticity between the recall of recent and remote fear extinction memory. Learn Mem 14, 520-24.
39. Milad, M. R., and Quirk, G. J. (2002) Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 420, 70-74.
40. Kim, J. J., and Fanselow, M. S. (1992) Modality-specific retrograde amnesia of fear. Science 256, 675-77.
41. Wilson, A., Brooks, D. C., and Bouton, M. E. (1995) The role of the rat hippocampal system in several effects of context in extinction. Behav Neurosci 109, 255-60.
42. Frohardt, R. J., Guarraci, F. A., and Bouton, M. E. The effects of neurotoxic hippocampal lesions on two effects of context after fear extinction. Behav Neurosci 114, 227-40.
43. Isiegas, C., Park, A., Kandel, E. R., Abel, T., and Lattal, K. M. (2006) Transgenic inhibition of neuronal protein kinase A activity facilitates fear extinction. J Neurosci 26, 12700-7.
44. Fischer, A., Sananbenesi, F., Schrick, C., Spiess, J., and Radulovic, J. (2004) Distinct roles of hippocampal de novo protein synthesis and actin rearrangement in extinction of contextual fear. J Neurosci 24, 1962-66.
45. Fischer, A., Radulovic, M., Schrick, C., Sananbenesi, F., Godovac-Zimmermann, J., and Radulovic, J. (2006) Hippocampal Mek/Erk signaling mediates extinction of contextual freezing behavior. Neurobiol Learn Mem 87, 149-58.
46. Cammarota, M., Bevilaqua, L. R., Kerr, D., Medina, J. H., and Izquierdo, I. (2003) Inhibition of mRNA and protein synthesis in the CA1 region of the dorsal hippocampus blocks reinstallment of an extinguished conditioned fear response. J Neurosci 23, 737-41.
47. Harris, J. A., and Westbrook, R. F. (2001) Evidence that GABA transmission mediates context-specific extinction of learned fear. Psychopharmacology 140, 105-15.
48. Corcoran, K. A., Desmond, T. J., K.A., F., and Maren, S. (2005) Hippocampal inactivation disrupts the acquisition and contextual encoding of fear extinction. J Neurosci 25, 9821-25.
49. McGaugh, J. L., Castellano, C., and Brioni, J. (1990) Picrotoxin enhances latent extinction of conditioned fear. Behav Neurosci 104, 264-67.
50. Berlau, D. J., and McGaugh, J. L. (2006) Enhancement of extinction memory consolidation: the role of the noradrenergic and GABAergic systems within the basolateral amygdala. Neurobiol Learn Mem 86, 123-32.
51. Chhatwal, J. P., Myers, K. M., Ressler, K. J., and Davis, M. (2005) Regulation of gephyrin and GABAA receptor binding within the amygdala after fear acquisition and extinction. J Neurosci 25, 502-6.
52. Ressler, K. J., Paschall, G., Zhou, X. L., and Davis, M. (2002) Regulation of synaptic plasticity genes during consolidation of fear conditioning J Neurosci 15, 7892-7902.
53. Cammarota, M., Bevilaqua, L. R., Rossato, J. I., Ramirez, M., Medina, J. H., and Izquierdo, I. (2005) Relationship between short-and long-term memory and short-and long-term extinction. Neurobiol Learn Mem 84, 25-32.
54. Borowski, T. B., and Kokkinidis, L. (1996) Contribution of ventral tegmental area dopamine neurons to expression of conditional fear: effects of electrical stimulation, excitotoxin lesions, and quinpirole infusion on potentiated startle in rats. Behav Neurosci 110, 1349-64.
55. Borowski, T. B., and Kokkinidis, L. (1998) The effects of cocaine, amphetamine, and the dopamine D1 receptor agonist SKF 38393 on fear extinction as measured with potentiated startle: implications for psychomotor stimulant psychosis. Behav Neurosci 112, 952-65.
56. Pezze, M. A., and Feldon, J. (2004) Mesolimbic dopaminergic pathways in fear conditioning. Prog Neurobiol 74, 301-20.
57. Willick, M. L., and Kokkinidis, L. (1995) Cocaine enhances the expression of fearpotentiated startle: evaluation of state-dependent extinction and the shock-sensitization of acoustic startle. Behav Neurosci 109, 929-38.
58. Nader, K., and LeDoux, J. (1999) The dopaminergic modulation of fear: quinpirole impairs the recall of emotional memories in rats. Behav Neurosci 113, 152-65.
59. Ponnusamy, R., Nissim, H. A., and Barad, M. (2005) Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice. Learn Mem 12, 399-406.
60. El-Ghundi, M., O'Dowd, B. F., and George, S. R. (2001) Prolonged fear responses in mice lacking dopamine D1 receptor. Brain Res 892, 86-93.
61. Marsicano, G., Wotjak, C. T., Azad, S. C., et al. (2002) The endogenous cannabinoid system controls extinction of aversive memories. Nature 418, 530-34.
62. Suzuki, A., Josselyn, S. A., Frankland, P. W., Masushige, S., Silva, A. J., and Kida, S. (2004) Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J Neurosci 24, 4787-95.
63. Chhatwal, J. P., Davis, M., Maguschak, K. A., and Ressler, K. J. (2005) Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacology 30, 516-24.
64. McDonald, A. J., and Mascagni, F. (2001) Localization of the CB1 type cannabinoid receptor in the rat basolateral amygdala: high concentrations in a subpopulation of cholecystokinin-containing interneurons. Neuroscience 107, 641-52.
65. Azad, S. C., Eder, M., Marsicano, G., Lutz, B., Zieglgänsberger, W., and Rammes, G. (2003) Activation of the cannabinoid receptor type 1 decreases glutamatergic and GABAergic synaptic transmission in the lateral amygdala of the mouse. Learn Mem 10, 116-28.
66. Domenici, M. R., Azad, S. C., Marsicano, G., et al. (2006) Cannabinoid receptor type 1 located on presynaptic terminals of principal neurons in the forebrain controls glutamatergic synaptic transmission. J Neurosci 26, 5794-99.
67. Katona, I., Sperlágh, B., Maglóczky, Z., et al. (2000) GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus. Neuroscience 100, 797-804.
68. Cannich, A., Wotjak, C. T., Kamprath, K., Hermann, H., Lutz, B., and Marsicano, G. (2004) CB1 cannabinoid receptors modulate kinase and phosphatase activity during extinction of conditioned fear in mice. Learn Mem 11, 625-32.
69. Kamprath, K., Marsicano, G., Tang, J., et al. (2006) Cannabinoid CB1 receptor mediates fear extinction via habituation-like processes. J Neurosci 26, 6677-86.
70. Wang, H., Ferguson, G. D., Pineda, V. V., Cundiff, P. E., and Storm, D. R. (2004) Overexpression of type-1 adenylyl cyclase in mouse forebrain enhances recognition memory and LTP. Nat Neurosci 7, 635-42.
71. Korte, M., Minichiello, L., Klein, R., and Bonhoeffer, T. (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci U S A 92, 8856-60.
72. Alonso, M., Vianna, M. R., Depino, A. M., et al. (2002) BDNF-triggered events in the rat hippocampus are required for both short-and long-term memory formation. Hippocampus 12, 551-60.
73. Chhatwal, J. P., Stanek-Rattiner, L., Davis, M., and Ressler, K. J. (2006) Amygdala BDNF signaling is required for consolidation but not encoding of extinction. Nat Neurosci 9, 870-72.
74. Heldt, S. A., Stanek, L., Chhatwal, J. P., and Ressler, K. J. (2007) Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Mol Psychiatry 12, 656-70.
75. Sweatt, J. D. (2001) The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76, 1-10.
76. Sananbenesi, F., Fischer, A., Schrick, C., Spiess, J., and Radulovic, J. (2002) Phosphorylation of hippocampal Erk-1/2, Elk-1, and p90-Rsk-1 during contextual fear conditioning: interactions between Erk-1/2 and Elk-1 Mol Cell Neurosci 21, 463-76.
77. Atkins, C. M., Selcher, J. C., Petraitis, J. J., Trzaskos, J. M., and Sweatt, J. D. (1998) The MAPK cascade is required for mammalian associative learning. Nat Neurosci 1, 602-9.
78. Kelleher, R. J., 3rd, Govindarajan, A., Jung, H. Y., Kang, H., and Tonegawa, S. (2004) Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell 116, 467-79.
79. Chwang, W. B., O'Riordan, K. J., Levenson, J. M., and Sweatt, J. D. (2006) ERK/ MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning. Learn Mem 13, 322-28.
80. Levenson, J. M., and Sweatt, J. D. (2005) Epigenetic mechanisms in memory formation. Nat Rev 6, 108-19.
81. Levenson, J. M., O'Riordan, K. J., Brown, K. D., Trinh, M. A., Molfese, D. L., and Sweatt, J.D. (2004) Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 279, 40545-59.
82. Fischer, A., Sananbenesi, F., Wang, X., Dobbin, M., and Tsai, L. H. (2007) Recovery of learning and memory after neuronal loss is associated with chromatin remodeling. Nature 447, 178-82.
83. Schrick, C., Fischer, A., Srivastava, D., Tronson, N. C., Penzes, P., and Radulovic, J. (2007) N-cadherin regulates cytoskeletally associated IQGAP1/ERK signaling and memory formation. Neuron 55, 786-98.
84. Fukazawa, Y., Saitoh, Y., Ozawa, F., Ohta, Y., Mizuno, K., and Inokuchi, K. (2003) Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron 38, 447-60.
85. Huang, F., Chotiner, J. K., and Steward, O. (2007) Actin polymerization and ERK phosphorylation are required for Arc/Arg3.1 mRNA targeting to activated synaptic sites on dendrites. J Neurosci 27, 9054-67.
86. Plath, N., Ohana, O., Dammermann, B., et al. (2006) Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron 52, 437-44.
87. Silva, A. (2003) Molecular and cellular cognitive studies of the role of synpatic plasticity in memory. J Neurobiol 54, 224-37.
88. Bevilaqua, L. R., Medina, J. H., Izquierdo, I., and Cammarota, M. (2005) Memory consolidation induces N-methyl-D-aspartic acid-receptor-and Ca2 + /calmodulin-dependent protein kinase II-dependent modifications in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor properties. Neuroscience 136, 397-403.
89. Sananbenesi, F., Fischer, A., Schrick, C., Spiess, J., and Radulovic, J. (2003) Mitogenactivated protein kinase signaling in the hippocampus and its modulation by corticotropin-releasing factor receptor 2: a possible link between stress and fear memory. J Neurosci 23, 11436-43.
90. Amadio, M., Battaini, F., and Pascale, A. (2006) The different facets of protein kinases C: old and new players in neuronal signal transduction pathways. Pharmacol Res 54, 317-25.
91. Fischer, A., Sananbenesi, F., Spiess, J., and Radulovic, J. (2003) Cdk5 in the adult nondemented brain. Curr Drug Targets CNS Neurol Disord 6, 375-81.
92. Angelo, M., Plattner, F., and Giese, K. P. (2006) Cyclin-dependent kinase 5 in synaptic plasticity, learning and memory. J Neurochem 99, 353-70.
93. Samuels, B. A., Hsueh, Y. P., Shu, T., et al. (2007) Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron 56, 823-37.
94. Dhavan, R., and Tsai, L. H. (2001) A decade of CDK5. Nat Rev Mol Cell Biol 2, 749-59.
95. Fischer, A., Sananbenesi, F., Schrick, C., Spiess, J., and Radulovic, J. (2002) Cyclindependent kinase 5 is required for associative learning. J Neurosci 22, 3700-7.
96. Fischer, A., Sananbenesi, F., Schrick, C., Spiess, J., and Radulovic, J. (2003) Regulation of contextual fear conditioning by baseline and inducible septo-hippocampal cyclindependent kinase 5. Neuropharmacology 44, 1089-99.
97. Fischer, A., Sananbenesi, F., Pang, P. T., Lu, B., and Tsai, L. H. (2005) Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampusdependent memory. Neuron 48, 825-38.
98. Fu, W. Y., Chen, Y., Sahin, M., et al. (2007) Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Nat Neurosci 10, 67-76.
99. Ohshima, T., Ogura, H., Tomizawa, K., et al. (2005) Impairment of hippocampal longterm depression and defective spatial learning and memory in p35-/-mice. J Neurochem 10, 4159-68.
100. Patel, L. S., Wenzel, H. J., and Schwartkroin, P. A. (2004) Physiological and morphological characterization of dentate granule cells in the p35 knock-out mouse hippocampus: evidence for an epileptic circuit. J Neurosci 24, 9005-14.
101. Li, B. S., Sun, M. K., Zhang, L., et al. (2001) Regulation of NMDA receptors by cyclindependent kinase-5. Proc Natl Acad Sci U S A 98, 12742-47.
102. Wang, J., Liu, S., Fu, Y., Wang, J. H., and Lu, Y. (2003) Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors. Nat Neurosci 6, 1039-47.
103. Gong, X., Tang, X., Wiedmann, M., et al. (2003) Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis. Neuron 38, 33-46.
104. Kim, Y., Sung, J. Y., Ceglia., I, et al. (2006) Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology. Nature 442, 814-17.
105. Hawasli, A. H., Benavides, D. R., Nguyen, C., et al. (2007) Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. Nat Neurosci 10, 880-86.
106. Sananbenesi, F., Fischer, A., Wang, X., et al. (2007) A hippocampal Cdk5 pathway regulates extinction of contextual fear. Nat Neurosci 10, 1012-19.
107. Matus, A. (2000) Actin-based plasticity in dendritic spines. Science 290, 754-58.
108. Nakayama, A. Y., Harms, M. B., and Luo, L. (2000) Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci 20, 5329-38.
109. Hayashi, M. L., Choi, S. Y., Rao, B. S., et al. (2004) Altered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant-negative PAK transgenic mice. Neuron 42, 773-87.
110. Lei, M., Lu, W., Meng, W., et al. (2000) Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell 102, 387-97.
111. Yang, Y. L., and Lu, K. T. (2005) Facilitation of conditioned fear extinction by d-cycloserine is mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and requires de novo protein synthesis in basolateral nucleus of amygdala. Neuroscience 134, 247-60.
112. Lin, W. L., Lewis, J., Yen, S. H., Hutton, M., and Dickson, D. W. (2003) Filamentous tau in oligodendrocytes and astrocytes of transgenic mice expressing the human tau isoform with the P301L mutation. Am J Pathol 162, 213-18.
113. Genoux, D., Haditsch, U., Knobloch, M., Michalon, A., Storm, D., and Mansuy, I. M. (2002) Protein phosphatase 1 is a molecular constraint on learning and memory. Nature 418, 970-75.
114. Strahl, B. D., and Allis, C. D. (2000) The language of covalent histone modifications. Nature 403, 41-45.
115. Tsankova, N., Renthal, W., Kumar, A., and Nestler, E. J. (2007) Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 8, 355-67.
116. Lattal, K. M., Barrett, R. M., and Wood, M. A. (2007) Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Brain Res 121, 1125-31.
117. Bredy, T. W., Wu, H., Crego, C., Zellhoefer, J., Sun, Y. E., and Barad, M. (2007) Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn Mem 14, 268-76.
118. Bredy, T. W., and Barad, M. (2008) The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear. Learn Mem 15, 39-45.
119. Reijmers, L. G., Perkins, B. L., Matsuo, N., and Mayford, M. (2007) Localization of a stable neural correlate of associative memory. Science 317, 1230-3.