Neurons in medial prefrontal cortex signal memory for fear extinction
Abstract
Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.
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vmPFC activation during recall of extinction memory inhibits the amygdala and dampens fear expression.
“vmPFC activation during recall of extinction memory inhibits the amygdala and dampens fear expression”
From Childhood adversity and neural development: Deprivation and threat as distinct dimensions of early experience (2014) · cites this paper as Milad and Quirk, 2002
The prefrontal cortex is critical for extinction retention.
“This hypothesis was based on evidence that PFC (1) is critical for extinction retention (Herry and Garcia, 2003;Quirk et al, 2000;Milad and Quirk, 2002)”
From Impaired Extinction Retention in Adolescent Rats: Effects of D-Cycloserine (2010) · cites this paper as Milad and Quirk, 2002
Activity in rat prelimbic cortex underlies expression of conditioned fear, while activity in rat infralimbic cortex underlies extinction of conditioned fear.
“A number of studies on rats suggest that activity in PrL underlies the expression of conditioned fear (27, 40, 41), whereas activity in IL underlies the extinction of conditioned fear (10, 27, 41, 42).”
From Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders (2012) · cites this paper as [10]
Both rat infralimbic cortex and primate vmPFC play significant roles in successful recall of fear extinction.
“fear extinction studies suggest that both rat IL (10, 22, 27, 41, 42) and primate vmPFC (12, 15, 43) play a significant role in the successful recall of fear extinction.”
From Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders (2012) · cites this paper as [10]
Anticorrelations were found between the amygdala and medial prefrontal regions, including the dorsal and rostral ACC, consistent with the a priori hypothesis.
“Consistent with previous resting-state functional connectivity studies14,15 and effective connectivity studies,17,54 we found anticorrelations between the amygdala and medial prefrontal regions, including the dorsal and rostral ACC, consistent with our a priori hypothesis.”
From Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder (2012) · cites this paper as [54]
A lack of inhibition from dorsal medial regions to the amygdala can be interpreted as a deficit in automatic emotion regulation or a lack of cognitive control over emotion.
“Such a lack of inhibition from dorsal medial regions to the amygdala can be interpreted as a deficit in automatic emotion regulation10 or a lack of cognitive control over emotion.54”
From Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder (2012) · cites this paper as [54]
Electrical stimulation of infralimbic cortex reduces freezing to the conditioned stimulus even in animals that are resistant to extinction training.
“electrical stimulation of infralimbic cortex reduces freezing to the CS even in animals that are resistant to extinction training108,112.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [108]
Increased activity in the infralimbic cortex is associated with fear extinction.
“increased activity in the infralimbic cortex is associated with fear extinction108”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [108]
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“Its structure is comprised of many subnuclei, including the basolateral nuclei (BLA) and the central nucleus (Ce), which have distinct anatomical connections with other brain regions that serve different functions .”
BackgroundInfluentialNew Vistas on Amygdala Networks in Conditioned Fear
Paré, D., Quirk, G. J., & Ledoux, J. E. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00153.2004 · Cited by 841 · see citing works
Self-citationVertes, R. P. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.06.027 · Cited by 811 · see citing works
Developing constructs for psychopathology research: Research domain criteria
Sanislow, C. A., Pine, D. S., Quinn, K. J., Kozak, M. J., Garvey, M. A., Heinssen, R. K., Wang, P. S.-E., & Cuthbert, B. N. (2010) · Journal of Abnormal Psychology · doi:10.1037/a0020909 · Cited by 793 · see citing works
“Neural circuits connecting the basolateral amygdala with ventral medial areas of the prefrontal cortex are particularly important in the extinction of fear (Milad & Quirk, 2002; Pine, 2009).”
Shin, L. M., Orr, S. P., Carson, M. A., Rauch, S. L., Macklin, M. L., Lasko, N. B., Peters, P. M., Metzger, L. J., Dougherty, D. D., Cannistraro, P. A., et al. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.2.168 · Cited by 790 · see citing works
Emotion and the prefrontal cortex: an integrative review
Dixon, M. L., Thiruchselvam, R., Todd, R., & Christoff, K. (2017) · Psychological Bulletin · doi:10.1037/bul0000096 · Cited by 745 · see citing works
Resolving the neural circuits of anxiety
Calhoon, G. G., & Tye, K. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4101 · Cited by 766 · see citing works
Extinction circuits for fear and addiction overlap in prefrontal cortex
Peters, J., Kalivas, P. W., & Quirk, G. J. (2009) · Learning & Memory · doi:10.1101/lm.1041309 · Cited by 736 · see citing works
“Single-unit recordings reveal that CS responsiveness in IL-mPFC neurons develops only after extinction learning has occurred, and correlates with the degree of extinction recall (Milad and Quirk 2002).”
BackgroundSelf-citationAmygdala Microcircuits Controlling Learned Fear
Duvarci, S., & Pare, D. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.042 · Cited by 751 · see citing works
“Moreover, electrical stimulation of IL paired with CS onset reduces conditioned fear responses and accelerates the acquisition of extinction (Milad and Quirk, 2002).”
BackgroundVidal-Gonzalez, I., Vidal-Gonzalez, B., Rauch, S. L., & Quirk, G. J. (2006) · Learning & Memory · doi:10.1101/lm.306106 · Cited by 705 · see citing works
“IL microstimulation had the opposite effect, decreasing conditioned freezing and, under standard footshock conditions (Milad and Quirk 2002; Milad et al. 2004), facilitating extinction.”
BackgroundMethodResultInfluentialSelf-citationNeural circuitry underlying the regulation of conditioned fear and its relation to extinction
Delgado, M. R., Nearing, K. I., LeDoux, J. E., & Phelps, E. A. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.029 · Cited by 716 · see citing works
“…by the online manipulation of information characteristic of cognitive emotion regulation strategies (for review see Ochsner and Gross, 2005) influences amygdala function through connections to vmPFC regions that are also thought to inhibit the amygdala during extinction (Milad and Quirk, 2002).”
Prefrontal 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 · see citing works
“Farinelli M, Deschaux O, Hugues S, Thevenet A, Garcia R (in press): Hippocampal train stimulation modulates recall of fear extinction independently of prefrontal cortex synaptic plasticity and lesions.”
InfluentialSelf-citationMonk, C. S., Telzer, E. H., Mogg, K., Bradley, B. P., Mai, X., Louro, H. M. C., Chen, G., McClure-Tone, E. B., Ernst, M., & Pine, D. S. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.5.568 · Cited by 682 · see citing works
Fear Extinction and Relapse: State of the Art
Vervliet, B., Craske, M. G., & Hermans, D. (2013) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050212-185542 · Cited by 671 · see citing works
“Interestingly, the available research supports a much more consistent role for the hippocampal-vmPFC network in extinction recall (e.g., 24 hours later) than during initial extinction learning (Milad & Quirk 2002, Quirk et al. 2000).”
BackgroundContextual and temporal modulation of extinction: behavioral and biological mechanisms
Bouton, M. E., Westbrook, R. F., Corcoran, K. A., & Maren, S. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.12.015 · Cited by 671 · see citing works
Genetics of emotional regulation: the role of the serotonin transporter in neural function
Hariri, A. R., & Holmes, A. (2006) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2006.02.011 · Cited by 666 · see citing works
A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing
Tottenham, N. (2009) · Frontiers in Human Neuroscience · doi:10.3389/neuro.09.068.2009 · Cited by 651 · see citing works
“In particular, it has rich connections with the vmPFC (Amaral et al., 1992; Milad and Quirk, 2002; Ghashghaei et al., 2007) and hippocampus (Ikegaya et al.”
Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex
Covington, H. E., Lobo, M. K., Maze, I., Vialou, V., Hyman, J. M., Zaman, S., LaPlant, Q., Mouzon, E., Ghose, S., Tamminga, C. A., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1731-10.2010 · Cited by 621 · see citing works
“These findings are consistent with the observation that mPFC lesions induce hyper-sensitive stress responses and deficits in fear extinction (Holson, 1986; Silva et al., 1986; Diorio et al., 1993; Milad and Quirk, 2002).”
ResultLong-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species
Montay‐Gruel, P., Acharya, M. M., Petersson, K., Alikhani, L., Yakkala, C., Allen, B. D., Ollivier, J., Petit, B., Jorge, P. G., Syage, A. R., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901777116 · Cited by 603 · see citing works
“Deficits in this behavior have been linked to the infralimbic region of the mPFC and require active unlearning, thereby providing another measure of cognitive flexibility, or the ability to adapt to a changing environment (10, 47, 55, 56).”
BackgroundFear extinction in rats: Implications for human brain imaging and anxiety disorders
Milad, M. R., Rauch, S. L., Pitman, R. K., & Quirk, G. J. (2006) · Biological Psychology · doi:10.1016/j.biopsycho.2006.01.008 · Cited by 597 · see citing works
“However, given that stimulation of the vmPFC in rats was only effective when it was paired with conditioned stimuli (Milad and Quirk, 2002; Milad et al., 2004), rTMS might be significantly more effective when paired with traumatic reminders.”
BackgroundResultInfluentialSelf-citationStress and anxiety: Structural plasticity and epigenetic regulation as a consequence of stress
McEwen, B. S., Eiland, L., Hunter, R. G., & Miller, M. M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.07.014 · Cited by 596 · see citing works
“, 2003), plays an important role in fear extinction (Milad and Quirk, 2002; Morgan and LeDoux, 1995).”
BackgroundEisenberger, N. I., & Cole, S. W. (2012) · Nature Neuroscience · doi:10.1038/nn.3086 · Cited by 590 · see citing works
A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human
Soliman, F., Glatt, C. E., Bath, K. G., Levita, L., Jones, R. M., Pattwell, S. S., Jing, D., Tottenham, N., Amso, D., Somerville, L. H., et al. (2010) · Science · doi:10.1126/science.1181886 · Cited by 585 · see citing works
Emotion, Cognition, and Mental State Representation in Amygdala and Prefrontal Cortex
Salzman, C., & Fusi, S. (2010) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135256 · Cited by 581 · see citing works
“Increasing evidence implicates the amygdalaPFC circuit as playing a fundamental role in extinction (Gottfried & Dolan 2004, Izquierdo & Murray 2005, Likhtik et al. 2005, Milad & Quirk 2002, Olsson & Phelps 2004, Pare et al. 2004, Quirk et al. 2000).”
BackgroundThe default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas
Carhart-Harris, R. L., & Friston, K. J. (2010) · Brain · doi:10.1093/brain/awq010 · Cited by 574 · see citing works
“There is a huge amount of clinical and preclinical evidence supporting the limbic-suppressive function of the medial prefrontal cortex (Hariri et al., 2000; Milad and Quirk, 2002; Rosenkranz and Grace 2002; Phillips et al., 2003; Phelps et al., 2004; Etkin et al., 2006; Milad et al., 2006).”
BackgroundThe neuroscience of prejudice and stereotyping
Amodio, D. M. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3800 · Cited by 569 · see citing works
Burgos-Robles, A., Vidal-Gonzalez, I., & Quirk, G. J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0378-09.2009 · Cited by 530 · see citing works
“Failure to recall extinction results from deficient IL activity (Herry and Garcia, 2002; Milad and Quirk, 2002; Barrett et al., 2003; Burgos-Robles et al., 2007), but it may also result from excessive activity in PL.”
BackgroundSelf-citationLevin, R., & Nielsen, T. A. (2007) · Psychological Bulletin · doi:10.1037/0033-2909.133.3.482 · Cited by 554 · see citing works
Lane, R. D., Ryan, L., Nadel, L., & Greenberg, L. S. (2014) · Behavioral and Brain Sciences · doi:10.1017/s0140525x14000041 · Cited by 572 · see citing works
“…the two – and this has considerable importance in the present context, because reconsolidation is assumed to actually change components of the reactivated memory, whereas extinction is assumed to merely create a new memory that overrides the previously trained response (Milad & Quirk 2002).”
BackgroundA conceptual framework for the neurobiological study of resilience
Kalisch, R., Müller, M. B., & Tüscher, O. (2015) · Behavioral and Brain Sciences · doi:10.1017/s0140525x1400082x · Cited by 669 · see citing works
Burgos-Robles, A., Vidal-Gonzalez, I., Santini, E., & Quirk, G. J. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.021 · Cited by 516 · see citing works
“This replicates prior studies in which untreated rats show a large variability in extinction recall (Herry and Garcia, 2002; Milad and Quirk, 2002).”
Self-citationClinical Implications of Neuroscience Research in PTSD
van der Kolk, B. A. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1364.022 · Cited by 525 · see citing works
The Role of the Medial Prefrontal Cortex in the Conditioning and Extinction of Fear
Giustino, T. F., & Maren, S. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00298 · Cited by 519 · see citing works
“It has previously been demonstrated that pharmacological activation of the IL during extinction enhances long-term retention (Thompson et al., 2010; Chang and Maren, 2011) and that CS-evoked activity correlates with extinction recall (Milad and Quirk, 2002).”
BackgroundResultInfluentialNeural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review
Kim, J. J., & Jung, M. W. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.06.005 · Cited by 636 · see citing works
“Milad and Quirk (2002) have shown that neurons in rat infralimbic cortex signal extinction memory.”
BackgroundResultInfluentialMesolimbic dopaminergic pathways in fear conditioning
Pezze, M. A., & Feldon, J. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.09.004 · Cited by 510 · see citing works
Retrieval of emotional memories.
Buchanan, T. W. (2007) · Psychological bulletin · doi:10.1037/0033-2909.133.5.761 · Cited by 494 · see citing works
Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits
Ressler, K. J., Berretta, S., Bolshakov, V. Y., Rosso, I. M., Meloni, E. G., Rauch, S. L., & Carlezon, W. A. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00635-8 · Cited by 531 · see citing works
Changing Fear: The Neurocircuitry of Emotion Regulation
Hartley, C. A., & Phelps, E. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.121 · Cited by 489 · see citing works
“IL neurons show increased activity to the CS during extinction retrieval (Milad and Quirk, 2002).”
BackgroundRoles of NMDA NR2B Subtype Receptor in Prefrontal Long-Term Potentiation and Contextual Fear Memory
Zhao, M., Toyoda, H., Lee, Y., Wu, L., Ko, S. W., Zhang, X.-H., Jia, Y., Shum, F. W. F., Xu, H., Li, B.-M., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.08.014 · Cited by 495 · see citing works
“…cortex have projections to the amygdala (Cassell and Wright, 1986) and the role of the prefrontal cortex in fear extinction has been reported (Milad and Quirk, 2002; Santini et al., 2004), only a few conflicting results are available on the contributions of the prefrontal and/or ACC on fear…”
BackgroundKalisch, 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 · see citing works
“The ventromedial prefrontal cortex (VMPFC) is involved in the storage and recall of extinction memories (Morgan and LeDoux, 1995; Milad and Quirk, 2002; Phelps et al., 2004; Milad et al., 2005).”
BackgroundNeuronal circuits of fear extinction
Herry, C., Ferraguti, F., Singewald, N., Letzkus, J. J., Ehrlich, I., & Lüthi, A. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07101.x · Cited by 484 · see citing works
“Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience, 31, 599–612 plasticity in the IL is correlated with behavioural expression of extinction memory (Herry & Garcia, 2002, 2003; Milad & Quirk, 2002).”
BackgroundResultInfluentialBredy, T. W., Wu, H., Crego, C., Zellhoefer, J., Sun, Y. E., & Barad, M. (2007) · Learning & Memory · doi:10.1101/lm.500907 · Cited by 548 · see citing works
The storm and stress of adolescence: insights from human imaging and mouse genetics
Casey, B. J., Jones, R. M., Levita, L., Libby, V., Pattwell, S. S., Ruberry, E. J., Soliman, F., & Somerville, L. H. (2010) · Developmental Psychobiology · doi:10.1002/dev.20447 · Cited by 480 · see citing works
“…amygdala-vPFC network, showing imbalanced activity in adolescents, is consistent with a wide variety of work in animal (Baxter et al., 2000; Milad & Quirk, 2002) and human samples (Delgado et al., 2006; Etkin et al., 2006; Haas et al., 2007; Johnstone et al., 2007; Urry et al., 2006),…”
BackgroundResultAttachment figures activate a safety signal-related neural region and reduce pain experience
Eisenberger, N. I., Master, S. L., Inagaki, T. K., Taylor, S. E., Shirinyan, D., Lieberman, M. D., & Naliboff, B. D. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108239108 · Cited by 471 · see citing works
“Thus, in rats, stimulating the VMPFC while presenting a fearinducing cue diminishes fear responding, suggesting a role for this region in inhibiting the fear response (18).”
BackgroundImplications of memory modulation for post-traumatic stress and fear disorders
Parsons, R. G., & Ressler, K. J. (2013) · Nature Neuroscience · doi:10.1038/nn.3296 · Cited by 476 · see citing works
Ventromedial Prefrontal Cortex Is Critical for the Regulation of Amygdala Activity in Humans
Motzkin, J. C., Philippi, C. L., Wolf, R. C., Baskaya, M. K., & Koenigs, M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.02.014 · Cited by 454 · see citing works
“org/journal of rodent studies demonstrated a causal chain between activity in the infralimbic cortex (the purported homologue of human vmPFC), inhibition of the amygdala, and extinction of conditioned behavioral and physiologic fear responses (7,9,10,40).”
BackgroundAmygdala 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 · see citing works
Stress-induced prefrontal reorganization and executive dysfunction in rodents
Holmes, A., & Wellman, C. L. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.11.005 · Cited by 469 · see citing works
“In rats, 1 week of restraint was also found to impair extinction memory (Miracle et al., 2006), which is interesting in light of evidence that IL is preferentially recruited during extinction recall (Milad and Quirk, 2002).”
Izquierdo, A., Wellman, C. L., & Holmes, A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0474-06.2006 · Cited by 459 · see citing works
Dorsal Anterior Cingulate Cortex: A Bottom-Up View
Heilbronner, S. R., & Hayden, B. Y. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-013952 · Cited by 469 · see citing works
From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and anxiety disorders
VanElzakker, M. B., Kathryn Dahlgren, M., Caroline Davis, F., Dubois, S., & Shin, L. M. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.11.014 · Cited by 482 · see citing works
“Indeed, excitation of infralimbic cortex during presentation of a CS (Milad & Quirk, 2002) or in a fear context (Thompson et al., 2010) causes extinction.”
BackgroundMonk, C. S., Nelson, E. E., McClure, E. B., Mogg, K., Bradley, B. P., Leibenluft, E., Blair, R. J. R., Chen, G., Charney, D. S., Ernst, M., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.6.1091 · Cited by 458 · see citing works
“Concerning the second possibility, the ventral prefrontal cortex is involved in various regulatory processes (9, 35, 36).”
BackgroundThe structural integrity of an amygdala-prefrontal pathway predicts trait anxiety
Kim, M. J., & Whalen, P. J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2335-09.2009 · Cited by 433 · see citing works
“Evidence from the nonhuman animal literature indicates that the ventromedial prefrontal cortex (vmPFC), including the medial orbitofrontal cortex and ventral anterior cingulate cortex, is reciprocally connected with the amygdala, both functionally and anatomically (Amaral et al., 1992; Milad and Quirk, 2002; Ghashghae…”
BackgroundHow the Neurocircuitry and Genetics of Fear Inhibition May Inform Our Understanding of PTSD
Jovanović, T., & Ressler, K. J. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09071074 · Cited by 441 · see citing works
“Milad MR, Quirk GJ, Pitman RK, Orr SP, Fischl B, Rauch SL.”
BackgroundInfluential
- Authors
- Milad, M. R., & Quirk, G. J.
- Affiliations
- Ponce Health Sciences University (PR)
- Corresponding author
- Quirk, Gregory J.
- Venue
- Nature
- Published
- 2002-11
- Volume
- 420
- Issue
- 6911
- Pages
- 70-74
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1989045560
- Cited by
- 1,836
- References
- 30
- Citations by year
- 2026: 40 · 2025: 55 · 2024: 73 · 2023: 59 · 2022: 58 · 2021: 82 · 2020: 75 · 2019: 88 · 2018: 90 · 2017: 80 · 2016: 102 · 2015: 95 · 2014: 95 · 2013: 121 · 2012: 88
- FWCI
- 23.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- National Institute of Mental Health
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fear extinction, medial prefrontal cortex, infralimbic cortex, prelimbic cortex, memory extinction, fear conditioning, memory consolidation, neuronal firing, electrical stimulation, freezing behavior, rats
- MeSH terms
- Acoustic Stimulation, Animals, Conditioning, Classical, Electroshock, Extinction, Psychological, Fear, Male, Memory, Neurons, Sound, Rats, Sprague-Dawley, Prefrontal Cortex, Rats
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