The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Segregated Populations of Hippocampal Principal CA1 Neurons Mediating Conditioning and Extinction of Contextual Fear
Open accessAbstract
Learning processes mediating conditioning and extinction of contextual fear require activation of several key signaling pathways in the hippocampus. Principal hippocampal CA1 neurons respond to fear conditioning by a coordinated activation of multiple protein kinases and immediate early genes, such as cFos, enabling rapid and lasting consolidation of contextual fear memory. The extracellular signal-regulated kinase (Erk) additionally acts as a central mediator of fear extinction. It is not known however, whether these molecular events take place in overlapping or nonoverlapping neuronal populations. By using mouse models of conditioning and extinction of fear, we set out to determine the time course of cFos and Erk activity, their cellular overlap, and regulation by afferent cholinergic input from the medial septum. Analyses of cFos(+) and pErk(+) cells by immunofluorescence revealed predominant nuclear activation of either protein during conditioning and extinction of fear, respectively. Transgenic cFos-LacZ mice were further used to label in vivo Fos(+) hippocampal cells during conditioning followed by pErk immunostaining after extinction. The results showed that these signaling molecules were activated in segregated populations of hippocampal principal neurons. Furthermore, immunotoxin-induced lesions of medial septal neurons, providing cholinergic input into the hippocampus, selectively abolished Erk activation and extinction of fear without affecting cFos responses and conditioning. These results demonstrate that extinction mechanisms based on Erk signaling involve a specific population of CA1 principal neurons distinctively regulated by afferent cholinergic input from the medial septum.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“which, unlike cued extinction, requires direct involvement of the hippocampus (Tronson et al., 2009).”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Tronson et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Neuropsychology of Anxiety
Gray, J. A., & McNaughton, N. (2003) · doi:10.1093/acprof:oso/9780198522713.001.0001 · Cited by 1,953
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 · cited 2×
“Whereas the prefrontal cortex involves excitatory glutamatergic-mediated mechanisms to form new extinction memories (Milad and Quirk, 2002), and the amygdala recruits learning mechanisms involving both excitatory and inhibitory neurotransmission to regulate expression of fear (Falls et al.”
BackgroundContext and Behavioral Processes in Extinction: Table 1.
Bouton, M. E. (2004) · Learning & Memory · doi:10.1101/lm.78804 · Cited by 1,808
Neuronal signalling of fear memory
Maren, S., & Quirk, G. J. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1535 · Cited by 1,428
The MAPK cascade is required for mammalian associative learning
Atkins, C. M., Selcher, J. C., Petraitis, J. J., Trzaskos, J. M., & Sweatt, J. D. (1998) · Nature Neuroscience · doi:10.1038/2836 · Cited by 1,083
Mitogen-activated protein kinases in synaptic plasticity and memory
Sweatt, J. D. (2004) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2004.04.001 · Cited by 1,013
Switching 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
Localization of a Stable Neural Correlate of Associative Memory
Reijmers, L. G. J. E., Perkins, B. L., Matsuo, N., & Mayford, M. R. (2007) · Science · doi:10.1126/science.1143839 · Cited by 853
Extinction 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
Vinogradova, O. S. (2001) · Hippocampus · doi:10.1002/hipo.1073 · Cited by 550
Startle reactivity and anxiety disorders: aversive conditioning, context, and neurobiology
Grillon, C. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01665-7 · Cited by 514
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
Synaptic Protein Degradation Underlies Destabilization of Retrieved Fear Memory
Lee, S.-H., Choi, J.-H., Lee, N., Lee, H.-R., Kim, J.-I., Yu, N.-K., Choi, S.-L., Lee, S.-H., Kim, H., & Kaang, B.-K. (2008) · Science · doi:10.1126/science.1150541 · Cited by 409
Radulovic, J., Rühmann, A., Liepold, T., & Spiess, J. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-12-05016.1999 · Cited by 402
Fleischmann, A., Hvalby, Ø., Jensen, V., Strekalova, T. V., Zacher, C., Layer, L. E., Kvello, A., Reschke, M., Spanagel, R., Sprengel, R., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-27-09116.2003 · Cited by 385
Patterson, S. L., Pittenger, C., Morozov, A., Martin, K. C., Scanlin, H., Drake, C., & Kandel, E. R. (2001) · Neuron · doi:10.1016/s0896-6273(01)00443-3 · Cited by 334
Winder, D. G., Martin, K. C., Muzzio, I. A., Rohrer, D. K., Chruscinski, A. J., Kobilka, B. K., & Kandel, E. R. (1999) · Neuron · doi:10.1016/s0896-6273(00)81124-1 · Cited by 326
Spine-Type-Specific Recruitment of Newly Synthesized AMPA Receptors with Learning
Matsuo, N., Reijmers, L. G. J. E., & Mayford, M. R. (2008) · Science · doi:10.1126/science.1149967 · Cited by 311
Kovalovsky, D., Refojo, D., Liberman, A. C., Hochbaum, D., Páez-Pereda, M., Coso, O. A., Stalla, G. K., Holsboer, F., & ARZT, E. S. (2002) · Molecular Endocrinology · doi:10.1210/mend.16.7.0863 · Cited by 277
McClelland, J. L., & Goddard, N. (1996) · Hippocampus · doi:10.1002/(sici)1098-1063(1996)6:6 · Cited by 264
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
Radulović, J., Kammermeier, J., & Spiess, J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-18-07452.1998 · Cited by 245
Fos-IacZ transgenic mice: Mapping sites of gene induction in the central nervous system
Smeyne, R. J., Schilling, K., Robertson, L. M., Luk, D. C., Oberdick, J., Curran, T., & Morgan, J. I. (1992) · Neuron · doi:10.1016/0896-6273(92)90105-m · Cited by 242
Fischer, A., Sananbenesi, F., Schrick, C., Spiess, J., & Radulović, J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5112-03.2004 · Cited by 222
Szapiro, G., Vianna, M. R. M., McGaugh, J. L., Medina, J. H., & Izquierdo, I. (2003) · Hippocampus · doi:10.1002/hipo.10043 · Cited by 221
BERLAU, D., & MCGAUGH, J. (2006) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2005.12.008 · Cited by 220
Chhatwal, J. P., Myers, K. M., Ressler, K. J., & Davis, M. E. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3301-04.2005 · Cited by 214
Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 during Fear Conditioning
Sindreu, C. B., Scheiner, Z. S., & Storm, D. R. (2007) · Neuron · doi:10.1016/j.neuron.2006.11.024 · Cited by 195
PI3 kinase signaling is required for retrieval and extinction of contextual memory
Chen, X., Garelick, M. G., Wang, H., Li, V., Athos, J., & Storm, D. R. (2005) · Nature Neuroscience · doi:10.1038/nn1482 · Cited by 189
Trifilieff, P., Herry, C., Vanhoutte, P., Caboche, J., Desmedt, A., Riedel, G., Mons, N. E., & Micheau, J. (2006) · Learning & Memory · doi:10.1101/lm.80206 · Cited by 176
A hippocampal Cdk5 pathway regulates extinction of contextual fear
Sananbenesi, F., Fischer, A., Wang, X., Schrick, C., Neve, R. L., Radulović, J., & Tsai, L. (2007) · Nature Neuroscience · doi:10.1038/nn1943 · Cited by 143
Sananbenesi, F. (2002) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2002.1188 · Cited by 114
Hippocampal Mek/Erk signaling mediates extinction of contextual freezing behavior
Fischer, A., Radulović, M., Schrick, C., Sananbenesi, F., Godovac‐Zimmermann, J., & Radulović, J. (2006) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2006.08.003 · Cited by 108
N-Cadherin Regulates Cytoskeletally Associated IQGAP1/ERK Signaling and Memory Formation
Schrick, C., Fischer, A., Srivastava, D. P., Tronson, N. C., Penzes, P., & Radulović, J. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.034 · Cited by 98
Schilling, K., Luk, D. C., Morgan, J. I., & Curran, T. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.13.5665 · Cited by 95
A requirement for memory retrieval during and after long-term extinction learning
Ouyang, M., & THOMAS, S. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502315102 · Cited by 94
Targeted ablation of diverse cell classes in the nervous system in vivo
Nirenberg, S., & Cepko, C. L. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-08-03238.1993 · Cited by 89
Phosphorylation of extra-nuclear ERK/MAPK is required for long-term memory consolidation in the crab
Feld, M., Dimant, B., Delorenzi, A., Coso, O. A., & Romano, A. G. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.09.005 · Cited by 87
Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior
Tronson, N. C., Schrick, C., Fischer, A., Sananbenesi, F., Pagès, G., Pouysségur, J., & Radulović, J. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301550 · Cited by 86
Wheal, H. V., & Miller, J. J. (1980) · Brain Research · doi:10.1016/0006-8993(80)90837-9 · Cited by 86
Ryu, J., Futai, K., Feliú-Mójer, M. I., Weinberg, R. J., & Sheng, M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1944-08.2008 · Cited by 84
Transgenic Inhibition of Neuronal Protein Kinase A Activity Facilitates Fear Extinction
Isiegas, C., Park, A., Kandel, E. R., Abel, T. G., & Lattal, K. M. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2743-06.2006 · Cited by 75
cFos induction during conditioned taste aversion expression varies with aversion strength
Navarro, M., Spray, K. J., Cubero, I., Thiele, T. E., & Bernstein, I. L. (2000) · Brain Research · doi:10.1016/s0006-8993(00)03032-8 · Cited by 52
Brown, H. E., Garcia, M. M., & Harlan, R. E. (1998) · Brain Research Protocols · doi:10.1016/s1385-299x(98)00003-8 · Cited by 41
Fletcher, B. R., Baxter, M. G., Guzowski, J. F., Shapiro, M. L., & Rapp, P. R. (2007) · Hippocampus · doi:10.1002/hipo.20261 · Cited by 35
Rovira, C., Cherubini, E., & Ben‐Ari, Y. (1983) · Neuropharmacology · doi:10.1016/0028-3908(83)90015-1 · Cited by 26
Rovira, C., Cherubini, E., & Ben‐Ari, Y. (1982) · Neuropharmacology · doi:10.1016/0028-3908(82)90087-9 · Cited by 17
Research works printed but not linked: 1
- 10.1210/me.16.7.1638 · DOI
Cited by
Sorted by citations
Pape, H.-C., & Pare, D. (2010) · Physiological Reviews · doi:10.1152/physrev.00037.2009 · Cited by 994
Izquierdo, I., Furini, C. R. G., & Myskiw, J. C. (2016) · Physiological Reviews · doi:10.1152/physrev.00018.2015 · Cited by 453
Gating of Fear in Prelimbic Cortex by Hippocampal and Amygdala Inputs
Sotres-Bayón, F., Sierra‐Mercado, D., Pardilla‐Delgado, E., & Quirk, G. J. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.028 · Cited by 467
Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction
Rudenko, A., Dawlaty, M. M., Seo, J., Cheng, A. W., Meng, J., Le, T. T., Faull, K. F., Jaenisch, R., & Tsai, L. (2013) · Neuron · doi:10.1016/j.neuron.2013.08.003 · Cited by 450
Opposite effects of fear conditioning and extinction on dendritic spine remodelling.
Lai, C. S. W., Franke, T. F., & Gan, W.-B. (2012) · Nature · doi:10.1038/nature10792 · Cited by 392
Metadata
- Authors
- Tronson, N. C., Schrick, C., Guzman, Y. F., Huh, K. H., Srivastava, D. P., Penzes, P., Guedea, A. L., Gao, C., & Radulovic, J.
- Affiliations
- Northwestern University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-03-18
- Volume
- 29
- Issue
- 11
- Pages
- 3387-3394
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2892108
- OpenAlex
- W2109078253
- Cited by
- 136
- References
- 47
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 11 · 2020: 10 · 2019: 10 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 11 · 2014: 8 · 2013: 13 · 2012: 8
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Northwestern University
- National Institute of Mental Health (R01MH073669, MH073669)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- contextual fear, fear extinction, fear conditioning, CA1 pyramidal neurons, c-fos, extracellular signal-regulated kinase, ERK signaling, medial septum, cholinergic input, fear memory consolidation
- MeSH terms
- Animals, Conditioning, Psychological, Extinction, Psychological, Fear, Hippocampus, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
