The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
Dissociable Roles of Prelimbic and Infralimbic Cortices, Ventral Hippocampus, and Basolateral Amygdala in the Expression and Extinction of Conditioned Fear
Open accessAbstract
Current models of conditioned fear expression and extinction involve the basolateral amygdala (BLA), ventral medial prefrontal cortex (vmPFC), and the hippocampus (HPC). There is some disagreement with respect to the specific roles of these structures, perhaps due to subregional differences within each area. For example, growing evidence suggests that infralimbic (IL) and prelimbic (PL) subregions of vmPFC have opposite influences on fear expression. Moreover, it is the ventral HPC (vHPC), rather than the dorsal HPC, that projects to vmPFC and BLA. To help determine regional specificity, we used small doses of the GABA(A) agonist muscimol to selectively inactivate IL, PL, BLA, or vHPC in an auditory fear conditioning and extinction paradigm. Infusions were performed prior to extinction training, allowing us to assess the effects on both fear expression and subsequent extinction memory. Inactivation of IL had no effect on fear expression, but impaired the within-session acquisition of extinction as well as extinction memory. In contrast, inactivation of PL impaired fear expression, but had no effect on extinction memory. Inactivation of the BLA or vHPC impaired both fear expression and extinction memory. Post-extinction inactivations had no effect in any structure. We suggest a model in which amygdala-dependent fear expression is modulated by inputs from PL and vHPC, whereas extinction memory requires extinction-induced plasticity in IL, BLA, and/or vHPC.
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“Thus, stimulation of the infralimbic region should inhibit fear expression, and it does (Sierra-Mercado, Padilla-Coreano, & Quirk, 2011).”
From Learned helplessness at fifty: Insights from neuroscience. (2016) · cites this paper as Sierra-Mercado, Padilla-Coreano, & Quirk, 2011
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“Neither is vmPFC generally required for fear extinction (but see [36]), in which cues are presented without reinforcement and the CR diminishes over time [34].”
From Ventromedial prefrontal–subcortical systems and the generation of affective meaning (2012) · cites this paper as [36]
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Citations
Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585
Neurons in medial prefrontal cortex signal memory for fear extinction
Milad, M. R., & Quirk, G. J. (2002) · Nature · doi:10.1038/nature01138 · Cited by 1,836
Self-citationPhelps, E. A., Delgado, M. R., Nearing, K. I., & LeDoux, J. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.042 · Cited by 1,753
Neural Mechanisms of Extinction Learning and Retrieval
Quirk, G. J., & Mueller, D. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301555 · Cited by 1,645
Self-citationSmaller hippocampal volume predicts pathologic vulnerability to psychological trauma
Gilbertson, M. W., Shenton, M. E., Ciszewski, A., Kasai, K., Lasko, N. B., Orr, S. P., & Pitman, R. K. (2002) · Nature Neuroscience · doi:10.1038/nn958 · Cited by 1,635
(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.7.973 · Cited by 1,610
Differential projections of the infralimbic and prelimbic cortex in the rat
Vertes, R. P. (2004) · Synapse · doi:10.1002/syn.10279 · Cited by 1,550
Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat
Hoover, W. B., & Vertes, R. P. (2007) · Brain Structure and Function · doi:10.1007/s00429-007-0150-4 · Cited by 1,365
Neurobiological Basis of Failure to Recall Extinction Memory in Posttraumatic Stress Disorder
Milad, M. R., Pitman, R. K., Ellis, C. B., Gold, A. L., Shin, L. M., Lasko, N. B., Zeidan, M. A., Handwerger, K., Orr, S. P., & Rauch, S. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.06.026 · Cited by 1,339
Prefrontal cortex in the rat: Projections to subcortical autonomic, motor, and limbic centers
Gabbott, P. L. A., Warner, T. A., Jays, P. R. L., Salway, P., & Busby, S. J. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20738 · Cited by 1,227
Milad, M. R., Wright, C. I., Orr, S. P., Pitman, R. K., Quirk, G. J., & Rauch, S. L. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.10.011 · Cited by 1,197
Self-citationPitkänen, A., Pikkarainen, M., Nurminen, N., & Ylinen, A. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06738.x · Cited by 1,001
The role of ventromedial prefrontal cortex in the recovery of extinguished fear
Quirk, G. J., Russo, G. K., Barron, J. L., & Lebron, K. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06225.2000 · Cited by 957 · cited 5×
“Impaired retrieval of extinction could result from impaired acquisition of extinction and/or impaired consolidation of extinction (Quirk et al., 2000).”
InfluentialSelf-citationSwitching on and off fear by distinct neuronal circuits
Herry, C., Ciocchi, S., Senn, V., Demmou, L., Müller, C., & Lüthi, A. (2008) · Nature · doi:10.1038/nature07166 · Cited by 950
Quirk, G. J., Likhtik, E., Pelletier, J. G., & Paré, D. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-25-08800.2003 · Cited by 927
Self-citationExtinction of emotional learning: contribution of medial prefrontal cortex
Morgan, M. A., Romanski, L. M., & LeDoux, J. E. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90241-c · Cited by 897 · cited 1×
“Plasticity in the ventral medial prefrontal cortex (vmPFC) is important for the retrieval of extinction memory (Morgan et al., 1993; Milad and Quirk, 2002; Quirk et al., 2006; Sotres-Bayon et al., 2006), and the hippocampus is thought to mediate the contextual gating of extinction (Corcoran et al.,…”
Vidal-Gonzalez, I., Vidal-Gonzalez, B., Rauch, S. L., & Quirk, G. J. (2006) · Learning & Memory · doi:10.1101/lm.306106 · Cited by 705
Self-citationPrefrontal mechanisms in extinction of conditioned fear
Quirk, G. J., Garcia, R., & González-Lima, F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.010 · Cited by 682
Self-citationExtinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala
Falls, W., Miserendino, M., & Davis, M. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-03-00854.1992 · Cited by 673
Activity in Prelimbic Cortex Is Necessary for the Expression of Learned, But Not Innate, Fears
Corcoran, K. A., & Quirk, G. J. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.5327-06.2007 · Cited by 639
Self-citationBurgos-Robles, A., Vidal-Gonzalez, I., Santini, E., & Quirk, G. J. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.021 · Cited by 546
Self-citationBurgos-Robles, A., Vidal-Gonzalez, I., & Quirk, G. J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0378-09.2009 · Cited by 530
Self-citationPresence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study
Milad, M. R., Orr, S. P., Lasko, N. B., Chang, Y., Rauch, S. L., & Pitman, R. K. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2008.01.017 · Cited by 512
Kalisch, R., Korenfeld, E., Stephan, K. E., Weiskopf, N., Seymour, B., & Dolan, R. J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2021-06.2006 · Cited by 493
Consolidation of Fear Extinction Requires Protein Synthesis in the Medial Prefrontal Cortex
Santini, E., Ge, H., Ren, K., de Ortiz, S. P., & Quirk, G. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0786-04.2004 · Cited by 479
Self-citationAmygdala intercalated neurons are required for expression of fear extinction
Likhtik, E., Popa, D., Apergis-Schoute, J., Fidacaro, G. A., & Paré, D. (2008) · Nature · doi:10.1038/nature07167 · Cited by 474
Applying Learning Principles to the Treatment of Post‐Trauma Reactions
ROTHBAUM, B. O., & DAVIS, M. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1301.012 · Cited by 454
Sotres-Bayon, F., Cain, C. K., & LeDoux, J. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.012 · Cited by 433
Emotional Perseveration: An Update on Prefrontal-Amygdala Interactions in Fear ExtinctionPreprint
Sotres-Bayón, F., Bush, D. E. A., & LeDoux, J. E. (2004) · Learning & Memory · doi:10.1101/lm.79504 · Cited by 419
Muller, J., Corodimas, K. P., Fridel, Z., & LeDoux, J. E. (1997) · Behavioral Neuroscience · doi:10.1037//0735-7044.111.4.683 · Cited by 401
Hippocampal Inactivation Disrupts the Acquisition and Contextual Encoding of Fear Extinction
Corcoran, K., Desmond, T., Frey, K., & Maren, S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2246-05.2005 · Cited by 390
Amygdala and Ventral Hippocampus Contribute Differentially to Mechanisms of Fear and Anxiety.
McHugh, S. B., Deacon, R. M. J., Rawlins, J. N. P., & Bannerman, D. M. (2004) · Behavioral Neuroscience · doi:10.1037/0735-7044.118.1.63 · Cited by 384 · cited 1×
“It has been previously shown that vHPC lesions reduce anxiety (McHugh et al., 2004), but this is unlikely to explain reduced freezing given that we observed no effect of vHPC inactivation in our measure of anxiety.”
Muller, J., Corodimas, K. P., Fridel, Z., & LeDoux, J. E. (1997) · Behavioral Neuroscience · doi:10.1037/0735-7044.111.4.683 · Cited by 382 · cited 1×
“Reduced fear expression with BLA inactivation was expected, and agrees with previous inactivation studies (Muller et al., 1997; Maren and Holt, 2004).”
BREMNER, J. D., VERMETTEN, E., SCHMAHL, C., VACCARINO, V., VYTHILINGAM, M., AFZAL, N., GRILLON, C., & CHARNEY, D. S. (2005) · Psychological Medicine · doi:10.1017/s0033291704003290 · Cited by 370
An Inhibitory Interface Gates Impulse Traffic between the Input and Output Stations of the Amygdala
Royer, S., Martina, M., & Paré, D. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-23-10575.1999 · Cited by 350
Laurent, V., & Westbrook, R. F. (2009) · Learning & Memory · doi:10.1101/lm.1474609 · Cited by 311
Amygdalar NMDA Receptors are Critical for New Fear Learning in Previously Fear-Conditioned Rats
Lee, H. J., & Kim, J. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08444.1998 · Cited by 310
Sotres-Bayón, F., Bush, D. E. A., & LeDoux, J. E. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301316 · Cited by 298
Mueller, D., Porter, J. T., & Quirk, G. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3248-07.2008 · Cited by 284
Self-citationMaren, S., & Holt, W. G. (2004) · Behavioral Neuroscience · doi:10.1037/0735-7044.118.1.97 · Cited by 280
Wilensky, A. E., Schafe, G. E., & LeDoux, J. E. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-18-07059.2000 · Cited by 265
Amygdala depotentiation and fear extinction
Kim, J., Lee, S., Park, K., Hong, I., Song, B., Son, G. H., Park, H., Kim, W. R., Park, E. J., Choe, H. K., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710548105 · Cited by 261
Sierra‐Mercado, D., Corcoran, K. A., Lebrón‐Milad, K., & Quirk, G. J. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05014.x · Cited by 255
Self-citationLin, C.-H., Yeh, S.-H., Lu, H.-Y., & Gean, P.-W. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-23-08310.2003 · Cited by 251
Amygdala BDNF signaling is required for consolidation but not encoding of extinction
Chhatwal, J. P., Rattiner, L. M., Davis, M., & Ressler, K. J. (2006) · Nature Neuroscience · doi:10.1038/nn1718 · Cited by 243
Lesions of the Basal Amygdala Block Expression of Conditioned Fear But Not Extinction
Anglada-Figueroa, D., & Quirk, G. J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2600-05.2005 · Cited by 238
Self-citationLaviolette, S. R., Lipski, W. J., & Grace, A. A. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1168-05.2005 · Cited by 235
Lu, K., Walker, D. L., & Davis, M. E. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-16-j0005.2001 · Cited by 224
Extinction of auditory fear conditioning requires MAPK/ERK activation in the basolateral amygdala
Herry, C., Trifilieff, P., Micheau, J., Lüthi, A., & Mons, N. E. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04893.x · Cited by 217
Hobin, J. A., Ji, J.-Z., & Maren, S. (2006) · Hippocampus · doi:10.1002/hipo.20144 · Cited by 211
Royer, S., & Paré, D. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00455-4 · Cited by 210
Morrow, B. A., Elsworth, J. D., Rasmusson, A. M., & Roth, R. H. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00014-7 · Cited by 195
Involvement of the amygdala GABAergic system in the modulation of memory storage
Brioni, J. D., Nagahara, A. H., & McGaugh, J. L. (1989) · Brain Research · doi:10.1016/0006-8993(89)90945-1 · Cited by 194
Ishikawa, A., & Nakamura, S. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-31-09987.2003 · Cited by 185
Gilmartin, M. R., & McEchron, M. D. (2005) · Behavioral Neuroscience · doi:10.1037/0735-7044.119.6.1496 · Cited by 183
Sotres-Bayon, F., Díaz‐Mataix, L., Bush, D. E. A., & LeDoux, J. E. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn099 · Cited by 168
Akirav, I., Raizel, H., & Maroun, M. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04603.x · Cited by 160
Reduced posterior hippocampal volume in posttraumatic stress disorder
Bonne, O., Vythilingam, M., Inagaki, M., Wood, S., Neumeister, A., Nugent, A. C., Snow, J., Luckenbaugh, D. A., Bain, E. E., Drevets, W. C., et al. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0707 · Cited by 156
Chenard, B. L., Shalaby, I. A., Koe, B. K., Ronau, R. T., Butler, T. W., Prochniak, M. A., Schmidt, A. W., & Fox, C. B. (1991) · Journal of Medicinal Chemistry · doi:10.1021/jm00114a018 · Cited by 143
Laurent, V., & Westbrook, R. F. (2008) · Learning & memory (Cold Spring Harbor, N.Y.) · doi:10.1101/lm.1080108 · Cited by 133
Nakao (2005) · doi:10.1016/j.pscychresns.2005.04.003 · Cited by 132
A role for the prefrontal cortex in recall of recent and remote memories
Blum, S., Hebert, A. E., & Dash, P. (2006) · NeuroReport · doi:10.1097/01.wnr.0000201509.53750.bc · Cited by 127
Rescorla, R. A. (2003) · Learning & Behavior · doi:10.3758/bf03195975 · Cited by 122
The role of prefrontal cortex CB1 receptors in the modulation of fear memory
Lin, H.-C., Mao, S.-C., Su, C.-L., & Gean, P.-W. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhn075 · Cited by 119
Hugues, S., Deschaux, O., & Garcia, R. (2004) · Learning & Memory · doi:10.1101/lm.77704 · Cited by 117
Chang, C., Berke, J. D., & Maren, S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011971 · Cited by 115
Kim, J. H., & Richardson, R. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4736-07.2008 · Cited by 114
Hugues, S., Chessel, A., Léna, I., Marsault, R., & Garcia, R. (2006) · Synapse · doi:10.1002/syn.20291 · Cited by 114
Laurent, V., Marchand, A. R., & Westbrook, R. F. (2008) · Learning & Memory · doi:10.1101/lm.928208 · Cited by 112
Biedenkapp, J. C., & Rudy, J. W. (2008) · Learning & Memory · doi:10.1101/lm.1099109 · Cited by 97
Hugues, S., & Garcia, R. (2007) · Learning & Memory · doi:10.1101/lm.625407 · Cited by 83
Ifenprodil inhibition of the 5-Hydroxytryptamine3 receptor
McCool, B. A., & Lovinger, D. M. (1995) · Neuropharmacology · doi:10.1016/0028-3908(95)00030-a · Cited by 82
Ceglia, I., Carli, M., Baviera, M., Renoldi, G., Calcagno, E., & Invernizzi, R. W. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02704.x · Cited by 79
Garcia, R., Chang, C., & Maren, S. (2006) · Learning & Memory · doi:10.1101/lm.60406 · Cited by 70
Church, J., Fletcher, E. J., Baxter, K., & MacDonald, J. F. (1994) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1994.tb17017.x · Cited by 63
Arco, A. D., Segovia, G., & Mora, F. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1288-3 · Cited by 60
The effects of yohimbine and amphetamine on fear expression and extinction in rats
Mueller, D. T., Olivera-Figueroa, L. A., Pine, D. S., & Quirk, G. J. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1491-x · Cited by 49
Self-citationOrsini, C. A., & Maren, S. (2009) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2009.07.007 · Cited by 19
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- Amano T, Unal CT, Paré D (2009). Synaptic basis of fear extinction in the amygdala: role of intercalated (ITC) neurons. Soc Neurosci Abstr 680: 10.
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Metadata
- Authors
- Sierra-Mercado, D., Padilla-Coreano, N., & Quirk, G. J.
- Affiliations
- University of Puerto Rico, Medical Sciences Campus (PR)
- Corresponding author
- Quirk, Gregory J
- Venue
- Neuropsychopharmacology
- Published
- 2010-10-20
- Volume
- 36
- Issue
- 2
- Pages
- 529-538
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3005957
- OpenAlex
- W2108888119
- Cited by
- 1,190
- References
- 78
- Citations by year
- 2026: 50 · 2025: 61 · 2024: 80 · 2023: 73 · 2022: 78 · 2021: 109 · 2020: 78 · 2019: 77 · 2018: 90 · 2017: 78 · 2016: 75 · 2015: 90 · 2014: 88 · 2013: 84 · 2012: 50
- FWCI
- 31.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh081975-05)
- National Institute of Mental Health (MH-058883, R01-MH081975, R01MH058883, R37MH058883, MH081975, R36MH089296, R29MH058883)
- National Institute of General Medical Sciences (T34GM007821)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- fear conditioning, fear extinction, infralimbic cortex, prelimbic cortex, ventral hippocampus, basolateral amygdala, ventromedial prefrontal cortex, auditory fear conditioning, muscimol inactivation, memory extinction
- MeSH terms
- Amygdala, Animals, Conditioning, Operant, Extinction, Psychological, Fear, Male, Rats, Sprague-Dawley, Prefrontal Cortex, Rats, CA1 Region, Hippocampal
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