Encoding of contextual fear memory in hippocampal–amygdala circuit
Open accessAbstract
In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal–amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1–BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and synaptic potentiation in the vCA1–BA pathway. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context.
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Cites
The Organization of Behavior; A Neuropsychological Theory.
Attneave, F., B., M., & Hebb, D. O. (1950) · The American Journal of Psychology · doi:10.2307/1418888 · Cited by 5,146 · see citing works
Short-Term Synaptic Plasticity
Zucker, R. S., & Regehr, W. G. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.092501.114547 · Cited by 5,068 · see citing works
Neuronal circuits for fear and anxiety
Tovote, P., Fadok, J. P., & Lüthi, A. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3945 · Cited by 1,786 · see citing works
Optogenetic stimulation of a hippocampal engram activates fear memory recall
Liu, X., Ramirez, S., Pang, P. T., Puryear, C. B., Govindarajan, A., Deisseroth, K. A., & Tonegawa, S. (2012) · Nature · doi:10.1038/nature11028 · Cited by 1,669 · see citing works
The contextual brain: implications for fear conditioning, extinction and psychopathology
Maren, S., Phan, K. L., & Liberzon, I. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3492 · Cited by 1,547 · see citing works
Memory engrams: Recalling the past and imagining the future
Josselyn, S. A., & Tonegawa, S. (2020) · Science · doi:10.1126/science.aaw4325 · Cited by 1,087 · see citing works
A shared neural ensemble links distinct contextual memories encoded close in time
Cai, D. J., Aharoni, D. B., Shuman, T., Shobe, J. L., Biane, J. S., Song, W., Wei, B., Veshkini, M., La-Vu, M. Q., Lou, J. J., et al. (2016) · Nature · doi:10.1038/nature17955 · Cited by 947 · see citing works
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 · see citing works
Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat
Jung, M. W., Wiener, S. I., & McNaughton, B. L. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-12-07347.1994 · Cited by 818 · see citing works
Engram cells retain memory under retrograde amnesia
Ryan, T. J., Roy, D. S., Pignatelli, M., Arons, A. L., & Tonegawa, S. (2015) · Science · doi:10.1126/science.aaa5542 · Cited by 745 · see citing works
Midbrain circuits for defensive behaviour
Tovote, P., Esposito, M. S., Botta, P., Chaudun, F., Fadok, J. P., Marković, M., Wolff, S. B. E., Ramakrishnan, C., Fenno, L. E., Deisseroth, K. A., et al. (2016) · Nature · doi:10.1038/nature17996 · Cited by 739 · see citing works
Differential Control of Learning and Anxiety along the Dorsoventral Axis of the Dentate Gyrus
Kheirbek, M. A., Drew, L. J., Burghardt, N. S., Costantini, D. O., Tannenholz, L., Ahmari, S. E., Zeng, H., Fenton, A. A., & Hen, R. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.038 · Cited by 713 · see citing works
Guenthner, C. J., Miyamichi, K., Yang, H. H., Heller, H. C., & Luo, L. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.025 · Cited by 705 · see citing works
Josselyn, S. A., Köhler, S., & Frankland, P. W. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn4000 · Cited by 687 · see citing works
Ventral CA1 neurons store social memory
Okuyama, T., Kitamura, T., Roy, D. S., Itohara, S., & Tonegawa, S. (2016) · Science · doi:10.1126/science.aaf7003 · Cited by 657 · see citing works
The probability of transmitter release at a mammalian central synapse
Hessler, N. A., Shirke, A. M., & Malinow, R. (1993) · Nature · doi:10.1038/366569a0 · Cited by 617 · see citing works
A circuit mechanism for differentiating positive and negative associations
Namburi, P., Beyeler, A., Yorozu, S., Calhoon, G. G., Halbert, S. A., Wichmann, R., Holden, S. S., Mertens, K. L., Anahtar, M., Felix-Ortiz, A. C., et al. (2015) · Nature · doi:10.1038/nature14366 · Cited by 614 · see citing works
Memory Engram Cells Have Come of Age
Tonegawa, S., Liu, X., Ramirez, S., & Redondo, R. L. (2015) · Neuron · doi:10.1016/j.neuron.2015.08.002 · Cited by 613 · see citing works
Anxiety Cells in a Hippocampal-Hypothalamic Circuit
Jimenez, J., Su, K., Goldberg, A., Luna, V. M., Biane, J. S., Ordek, G., Zhou, P., Ong, S. K., Wright, M. A., Zweifel, L. S., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.016 · Cited by 606 · see citing works
CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala
Zhou, Y., Won, J., Karlsson, M. G., Zhou, M., Rogerson, T., Balaji, J., Neve, R. L., Poirazi, P., & Silva, A. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2405 · Cited by 577 · see citing works
Hippocampal Memory Traces Are Differentially Modulated by Experience, Time, and Adult Neurogenesis
Denny, C. A., Kheirbek, M. A., Alba, E. L., Tanaka, K. F., Brachman, R. A., Laughman, K. B., Tomm, N. K., Turi, G. F., Losonczy, A., & Hen, R. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.018 · Cited by 558 · see citing works
Dynamics of Retrieval Strategies for Remote Memories
Goshen, I., Brodsky, M., Prakash, R., Wallace, J. L., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.033 · Cited by 546 · see citing works
Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo
Maren, S., & Fanselow (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-11-07548.1995 · Cited by 499 · see citing works
A persistent postsynaptic modification mediates long-term potentiation in the hippocampus
Kauer, J. A., Malenka, R. C., & Nicoll, R. A. (1988) · Neuron · doi:10.1016/0896-6273(88)90148-1 · Cited by 497 · see citing works
Yiu, A. P., Mercaldo, V., Chen, Y., Richards, B. A., Rashid, A. J., Hsiang, H., Pressey, J. C., Mahadevan, V., Tran, M. M., Kushner, S. A., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.07.017 · Cited by 442 · see citing works
Monosynaptic Circuit Tracing with Glycoprotein-Deleted Rabies Viruses
Callaway, E. M., & Luo, L. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0409-15.2015 · Cited by 418 · see citing works
Schafe, G. E., Nadel, N. V., Sullivan, G. M., Harris, A. Z., & LeDoux, J. E. (1999) · Learning & Memory · doi:10.1101/lm.6.2.97 · Cited by 407 · see citing works
Cortical Representations Are Reinstated by the Hippocampus during Memory Retrieval
Tanaka, K. Z., Pevzner, A., Hamidi, A., Nakazawa, Y., Graham, J. A., & Wiltgen, B. J. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.037 · Cited by 403 · see citing works
Interregional synaptic maps among engram cells underlie memory formation
Choi, J., Sim, S.-E., Kim, J., Choi, D. I., Oh, J., Ye, S., Lee, J., Kim, T., Ko, H., Lim, C., et al. (2018) · Science · doi:10.1126/science.aas9204 · Cited by 382 · see citing works
Fanselow, M. S., & Kim, J. J. (1994) · Behavioral Neuroscience · doi:10.1037//0735-7044.108.1.210 · Cited by 360 · see citing works
Selective information routing by ventral hippocampal CA1 projection neurons
Ciocchi, S., Passecker, J., Malagon‐Vina, H., Mikuš, N., & Klausberger, T. (2015) · Science · doi:10.1126/science.aaa3245 · Cited by 344 · see citing works
Fanselow, M. S., & Kim, J. J. (1994) · Behavioral Neuroscience · doi:10.1037/0735-7044.108.1.210 · Cited by 337 · see citing works
Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences
Li, Y., Allen, W. E., Thompson, K. R., Tian, Q., Hsueh, B., Ramakrishnan, C., Wang, A.-C., Jennings, J. H., Adhikari, A., Halpern, C. H., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.010 · Cited by 326 · see citing works
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 296 · see citing works
Distinct Hippocampal Pathways Mediate Dissociable Roles of Context in Memory Retrieval
Xu, C., Krabbe, S., Gründemann, J., Botta, P., Fadok, J. P., Osakada, F., Saur, D., Grewe, B. F., Schnitzer, M. J., Callaway, E. M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.051 · Cited by 277 · see citing works
Bocchio, M., Nabavi, S., & Capogna, M. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.022 · Cited by 260 · see citing works
Engram Cell Excitability State Determines the Efficacy of Memory Retrieval
Pignatelli, M., Ryan, T. J., Roy, D. S., Lovett, C., Smith, L. M., Muralidhar, S., & Tonegawa, S. (2018) · Neuron · doi:10.1016/j.neuron.2018.11.029 · Cited by 259 · see citing works
Marek, R., Jin, J., Goode, T. D., Giustino, T. F., Wang, Q., Acca, G. M., Holehonnur, R., Ploski, J. E., Fitzgerald, P. J., Lynagh, T., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0073-9 · Cited by 226 · see citing works
Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala
Kim, W. B., & Cho, J.-H. (2017) · Neuron · doi:10.1016/j.neuron.2017.08.004 · Cited by 206 · see citing works
Self-citationSynapse-specific representation of the identity of overlapping memory engrams
Abdou, K., Shehata, M., Choko, K., Nishizono, H., Matsuo, M., Muramatsu, S., & Inokuchi, K. (2018) · Science · doi:10.1126/science.aat3810 · Cited by 188 · see citing works
Zhu, H., Pleil, K. E., Urban, D. J., Moy, S. S., Kash, T. L., & Roth, B. L. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.35 · Cited by 162 · see citing works
Zhou, Y., Zhu, H., Liu, Z., Chen, X., Su, X., Ma, C., Tian, Z. F., Huang, B. Y., Yan, E., Liu, X., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0524-y · Cited by 162 · see citing works
Kishi, T., Tsumori, T., Yokota, S., & Yasui, Y. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.20919 · Cited by 150 · see citing works
Rudy, J. W., & Matus-Amat, P. (2005) · Behavioral Neuroscience · doi:10.1037/0735-7044.119.1.154 · Cited by 147 · see citing works
Prefrontal-Periaqueductal Gray-Projecting Neurons Mediate Context Fear Discrimination
Rozeske, R. R., Jercog, D., Karalis, N., Chaudun, F., Khoder, S., Girard, D., Winke, N., & Herry, C. (2018) · Neuron · doi:10.1016/j.neuron.2017.12.044 · Cited by 143 · see citing works
Zhang, W. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00256-x · Cited by 137 · see citing works
Kim, W. B., & Cho, J.-H. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3579-16.2017 · Cited by 131 · see citing works
Self-citationArtificial Association of Pre-stored Information to Generate a Qualitatively New Memory
Ohkawa, N., Saitoh, Y., Suzuki, A. Z., Tsujimura, S., Murayama, E., Kosugi, S., Nishizono, H., Matsuo, M., Takahashi, Y., Nagase, M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.017 · Cited by 120 · see citing works
Improved specificity of hippocampal memory trace labeling
Cazzulino, A. S., Martinez, R., Tomm, N. K., & Denny, C. A. (2015) · Hippocampus · doi:10.1002/hipo.22556 · Cited by 52 · see citing works
HEBB, D. O. - The organization of behavior. A neuropsychological theory
Richardson, D. B. (1965) · Cited by 40 · see citing works
Zhang, C.-L., Houbaert, X., Lepleux, M., Deshors, M., Normand, E., Gambino, F., Herzog, É., & Humeau, Y. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0882-x · Cited by 28 · see citing works
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Forgetting as a form of adaptive engram cell plasticity
Ryan, T. J., & Frankland, P. W. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00548-3 · Cited by 182 · see citing works
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Terranova, J. I., Yokose, J., Osanai, H., Marks, W. D., Yamamoto, J., Ogawa, S. K., & Kitamura, T. (2022) · Neuron · doi:10.1016/j.neuron.2022.01.019 · Cited by 117 · see citing works
Ratigan, H. C., Krishnan, S., Smith, S., & Sheffield, M. E. J. (2023) · Nature Communications · doi:10.1038/s41467-023-42429-6 · Cited by 60 · see citing works
Colyer-Patel, K., Kuhns, L., Weidema, A., Lesscher, H., & Cousijn, J. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105038 · Cited by 54 · see citing works
“8 conditioning involve distinct processes (Kim and Cho, 2020; Sachella et al., 2021), although extinction appears to predominantly involve the prefrontal cortex (Kutlu et al.”
Background
- Authors
- Kim, W. B., & Cho, J.-H.
- Affiliations
- University of California, Riverside (US)
- Corresponding author
- Cho, Jun-Hyeong
- Venue
- Nature Communications
- Published
- 2020-03-13
- Volume
- 11
- Issue
- 1
- Pages
- 1382-1382
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7069961
- OpenAlex
- W3012431228
- Cited by
- 289
- References
- 51
- Citations by year
- 2026: 29 · 2025: 50 · 2024: 52 · 2023: 62 · 2022: 49 · 2021: 41 · 2020: 6
- FWCI
- 21.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01MH118339, R56MH113894)
- UC | UC Riverside | Academic Senate, University of California, Riverside (Initial Complement Funds)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- contextual fear memory, ventral CA1, basal amygdala, synaptic potentiation, monosynaptic connections, aversive stimuli, threat prediction
- MeSH terms
- Amnesia, Amygdala, Animals, Avoidance Learning, Behavior, Animal, Disease Models, Animal, Fear, Hippocampus, Learning, Memory, Mice, Inbred C57BL, Neural Pathways, Neuronal Plasticity, Neurons, Synapses, Mice, Knockout, CA1 Region, Hippocampal, Basolateral Nuclear Complex
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