A Role for Prefrontal Cortex in Memory Storage for Trace Fear Conditioning
Open accessAbstract
The prefrontal cortex has been shown to participate in the association of events separated by time. However, it is not known whether the prefrontal cortex stores the memory for these relationships. Trace conditioning is a form of classical conditioning in which a time gap separates the conditioned stimulus (CS) from the unconditioned stimulus (US), the association of which has been shown to depend on prefrontal activity. Here we demonstrate that inhibition of extracellular signal-regulated kinase (Erk) cascade (a biochemical pathway involved in long-term memory storage) in the rat medial prefrontal cortex did not interfere with memory encoding for trace fear conditioning but impaired memory retention. In addition, animals displayed impaired memory for the irrelevancy of the training context. Hippocampal Erk phosphorylation was found to have a later time course than prefrontal Erk phosphorylation after trace fear conditioning, indicating a direct role for the prefrontal cortex in associative memory storage for temporally separated events as well as in memory storage of relevancy.
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
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?
Evidence from single-cell recordings in rats documented that the mPFC is crucially involved in learning long-term storage of information associating multimodal but temporally disconnected events.
“Evidence from singlecell recordings in rats [Runyan et al., 2004] documented that the mPFC is crucially involved in the learning of longterm storage of information associating multimodal but temporally disconnected events.”
From Social cognition and the brain: A meta-analysis (2009) · cites this paper as Runyan et al., 2004
The Discussion (pp. 1288–1295) says the rat mPFC stores long-term memory for trace fear conditioning, a multimodal task linking events separated in time. But the Abstract and “Role of mPFC in memory storage” section describe Erk inhibition, immunohistochemistry, and behavioral testing—not single-cell recordings. The finding is supported; the attributed recording method is not. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. (1995) · Psychological Review · doi:10.1037/0033-295x.102.3.419 · Cited by 5,256 · see citing works
Modality-Specific Retrograde Amnesia of Fear
Kim, J. J., & Fanselow, M. S. (1992) · Science · doi:10.1126/science.1585183 · Cited by 2,483 · see citing works
Classical conditioning and brain systems: the role of awareness
Clark, R. E., & Squire, L. R. (1998) · Science · doi:10.1126/science.280.5360.77 · Cited by 1,138 · see citing works
Dias, R., Robbins, T. W., & Roberts, A. C. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-23-09285.1997 · Cited by 555 · see citing works
Martin, K. C., Michael, D., Rose, J. C., Barad, M., Casadio, A., Zhu, H., & Kandel, E. R. (1997) · Neuron · doi:10.1016/s0896-6273(00)80330-x · Cited by 545 · see citing works
Filtering of neural signals by focused attention in the monkey prefrontal cortex
Everling, S., Tinsley, C. J., Gaffan, D., & Duncan, J. (2002) · Nature Neuroscience · doi:10.1038/nn874 · Cited by 224 · see citing works
Medial prefrontal cortex and Pavlovian conditioning: Trace versus delay conditioning.
McLaughlin, J., Skaggs, H., Churchwell, J., & Powell, D. A. (2002) · Behavioral Neuroscience · doi:10.1037/0735-7044.116.1.37 · Cited by 134 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Coggeshall RE, Lekan HA (1996) Methods for determining numbers of cells and synapses: a case for more uniform standards of review. J Comp Neu- rol 364:6 -15.
- Pavlov IP (1927) Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. London: Oxford UP.
- Shallice T (1988) From neuropsychology to mental structure. New York: Cambridge UP.
Cited by
Sorted by citations
Emotional processing in anterior cingulate and medial prefrontal cortex
Etkin, A., Egner, T., & Kalisch, R. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.11.004 · Cited by 3,059 · see citing works
Social cognition and the brain: A meta-analysis
Van Overwalle, F. (2009) · Human Brain Mapping · doi:10.1002/hbm.20547 · Cited by 1,792 · see citing works
The role of medial prefrontal cortex in memory and decision making
Euston, D. R., Gruber, A. J., & McNaughton, B. L. (2012) · Neuron · doi:10.1016/j.neuron.2012.12.002 · Cited by 1,541 · see citing works
Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress
Milad, M. R., & Quirk, G. J. (2012) · Annual Review of Psychology · doi:10.1146/annurev.psych.121208.131631 · Cited by 1,466 · see citing works
Prefrontal involvement in the regulation of emotion: convergence of rat and human studies
Quirk, G. J., & Beer, J. S. (2006) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.07.004 · Cited by 701 · see citing works
DNA methylation changes in plasticity genes accompany the formation and maintenance of memory
Halder, R., Hennion, M., Vidal, R. O., Shomroni, O., Rahman, R.-U., Rajput, A., Centeno, T. P., van Bebber, F., Capece, V., Vizcaino, J. C. G., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4194 · Cited by 358 · see citing works
Barsegyan, A., Mackenzie, S. M., Kurose, B. D., McGaugh, J. L., & Roozendaal, B. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1011975107 · Cited by 262 · see citing works
Modeling fragile X syndrome in the <i>Fmr1</i> knockout mouse
Kazdoba, T. M., Leach, P. T., Silverman, J. L., & Crawley, J. N. (2014) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2014.01024 · Cited by 241 · see citing works
Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear
Choi, D. C., Maguschak, K. A., Ye, K., Jang, S.-W., Myers, K. M., & Ressler, K. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909359107 · Cited by 212 · see citing works
Zhao, M.-G., Ko, S. W., Wu, L.-J., Toyoda, H., Xu, H., Quan, J., Li, J., Jia, Y., Ren, M., Xu, Z. C., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2103-06.2006 · Cited by 197 · see citing works
Nagai, T., Takuma, K., Kamei, H., Ito, Y., Nakamichi, N., Ibi, D., Nakanishi, Y., Murai, M., Mizoguchi, H., Nabeshima, T., et al. (2007) · Learning & Memory · doi:10.1101/lm.461407 · Cited by 184 · see citing works
Mannella, F., Gurney, K., & Baldassarre, G. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00135 · Cited by 166 · see citing works
Hylin, M. J., Orsi, S. A., Moore, A. N., & Dash, P. K. (2013) · Learning & Memory · doi:10.1101/lm.030197.112 · Cited by 143 · see citing works
Self-citationAdrenal stress hormones, amygdala activation, and memory for emotionally arousing experiences
Roozendaal, B., Barsegyan, A., & Lee, S. (2007) · Progress in Brain Research · doi:10.1016/s0079-6123(07)67006-x · Cited by 154 · see citing works
Bridging the interval: Theory and neurobiology of trace conditioning
Raybuck, J. D., & Lattal, K. M. (2014) · Behavioural Processes · doi:10.1016/j.beproc.2013.08.016 · Cited by 114 · see citing works
The role of awareness in delay and trace fear conditioning in humans
KNIGHT, D. C., NGUYEN, H. T., & BANDETTINI, P. A. (2006) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/cabn.6.2.157 · Cited by 83 · see citing works
Raybuck, J. D., & Gould, T. J. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06580.x · Cited by 53 · see citing works
Koh, M. T., Shao, Y., Sherwood, A., & Smith, D. R. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.01.023 · Cited by 51 · see citing works
Genetic background differences and nonassociative effects in mouse trace fear conditioning.
Smith, D. R., Gallagher, M., & Stanton, M. E. (2007) · Learning & Memory · doi:10.1101/lm.614807 · Cited by 47 · see citing works
- Authors
- Runyan, J. D., Moore, A. N., & Dash, P. K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-02-11
- Volume
- 24
- Issue
- 6
- Pages
- 1288-1295
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6730343
- OpenAlex
- W2167248961
- Cited by
- 224
- References
- 7
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 9 · 2019: 11 · 2018: 6 · 2017: 8 · 2016: 11 · 2015: 13 · 2014: 15 · 2013: 18 · 2012: 10
- FWCI
- 7.40
- 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
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 35457, R01NS035457)
- 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
- prefrontal cortex, trace fear conditioning, memory storage, memory retention, ERK signaling, long-term memory, hippocampus, contextual memory, temporal association, memory encoding, medial prefrontal cortex
- MeSH terms
- Animals, Association, Conditioning, Classical, Drug Administration Routes, Electroshock, Enzyme Inhibitors, Fear, Gyrus Cinguli, Hippocampus, Immunohistochemistry, Male, Memory, Phosphorylation, Retention, Psychology, Time Factors, Blotting, Western, Rats, Sprague-Dawley, Prefrontal Cortex, Mitogen-Activated Protein Kinases, Rats
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
