The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Synaptic Targeting of Double-Projecting Ventral CA1 Hippocampal Neurons to the Medial Prefrontal Cortex and Basal Amygdala
Open accessAbstract
The acquisition and retrieval of contextual fear memory requires coordinated neural activity in the hippocampus, medial prefrontal cortex (mPFC), and amygdala. The contextual information encoded in the hippocampus is conveyed to the mPFC and amygdala for contextual fear conditioning. Previous studies have suggested that a CA1 neuronal population in the ventral hippocampus (VH) projects to both the mPFC and amygdala and is recruited in context-dependent control of conditioned fear. However, how double-projecting ventral CA1 hippocampal (vCA1) neurons modulate the activity of the mPFC and amygdala at the synaptic level has not been determined previously. Here, we show that the optogenetic silencing of the VH prevented the recall of contextual fear memory in mice, indicating its role in contextual fear expression. In dual retrograde viral tracing and c-Fos immunostaining experiments, we found that a proportion of vCA1 neurons projected to both the mPFC and amygdala and were recruited preferentially during context exposure, suggesting their role in encoding context representations. Moreover, optogenetic stimulation of axon collaterals of double-projecting vCA1 neurons induced monosynaptic excitatory responses in both the mPFC and basal amygdala, indicating that they could convey contextual information through the VH–mPFC and VH–amygdala pathways. The activation of double-projecting vCA1 neurons also induced action potential firings in the mPFC neurons that project to the amygdala, suggesting that they can also activate the VH–mPFC–amygdala pathway. With these synaptic mechanisms, double-projecting vCA1 neurons could induce synchronized neural activity in the mPFC and amygdala and convey contextual information efficiently to the basal amygdala for contextual fear conditioning. SIGNIFICANCE STATEMENT This work demonstrates that ventral CA1 hippocampal (vCA1) neurons projecting to both the medial prefrontal cortex (mPFC) and amygdala are activated preferentially when contextual information is processed in the ventral hippocampus, which is required for contextual fear expression. Our electrophysiological experiments reveal that the activation of double-projecting vCA1 neurons induces excitatory synaptic activity in both the mPFC and amygdala. These results suggest that double-projecting vCA1 neurons could contribute to contextual fear responses by inducing synchronized activity in the mPFC and amygdala and conveying contextual information to the basal amygdala more efficiently than vCA1 neurons projecting to either the mPFC or amygdala alone. These findings provide important insights into the mechanisms of the acquisition and retrieval of contextual fear memory.
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“Inhibition of double-projecting vHPC neurons to the mPFC and basolateral amygdala (BLA) interferes with contextual threat recall [42]”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [42]
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
Millisecond-timescale, genetically targeted optical control of neural activity
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., & Deisseroth, K. A. (2005) · Nature Neuroscience · doi:10.1038/nn1525 · Cited by 5,015
Functional organization of the hippocampal longitudinal axis
Strange, B. A., Witter, M. P., Lein, E. S., & Moser, E. I. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3785 · Cited by 1,738
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
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
High-performance genetically targetable optical neural silencing by light-driven proton pumps
Chow, B. Y., Han, X., Dobry, A. S., Qian, X., Chuong, A. S., Li, M., Henninger, M. A., Belfort, G. M., Lin, Y., Monahan, P. E., et al. (2010) · Nature · doi:10.1038/nature08652 · Cited by 1,188
Pitkänen, 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
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 844
Time cells in the hippocampus: a new dimension for mapping memories
Eichenbaum, H. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3827 · Cited by 843
Jay, T. M., & Witter, M. P. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903130404 · Cited by 841
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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 633
Prefrontal cortex, amygdala, and threat processing: implications for PTSD
Alexandra Kredlow, M., Fenster, R. J., Laurent, E. S., Ressler, K. J., & Phelps, E. A. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01155-7 · Cited by 346
“Inhibition of double-projecting vHPC neurons to the mPFC and basolateral amygdala (BLA) interferes with contextual threat recall [42] and disconnection of the vHPC from the mPFC interferes with renewal of threat memories, a context-dependent process [43].”
BackgroundEncoding of contextual fear memory in hippocampal–amygdala circuit
Kim, W. B., & Cho, J.-H. (2020) · Nature Communications · doi:10.1038/s41467-020-15121-2 · Cited by 289
Self-citationThe mouse prefrontal cortex: Unity in diversity
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Metadata
- Authors
- Kim, W. B., & Cho, J.-H.
- Affiliations
- University of California, Riverside (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2017-04-06
- Volume
- 37
- Issue
- 19
- Pages
- 4868-4882
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6596479
- OpenAlex
- W2604657615
- Cited by
- 131
- References
- 42
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 10 · 2023: 23 · 2022: 17 · 2021: 20 · 2020: 16 · 2019: 11 · 2018: 9 · 2017: 3
- FWCI
- 6.12
- 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)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- University of California, Riverside
- 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
- ventral hippocampus, medial prefrontal cortex, basal amygdala, contextual fear memory, fear conditioning, synaptic targeting, axon collaterals, optogenetic silencing, c-fos
- MeSH terms
- Animals, Avoidance Learning, Conditioning, Classical, Extinction, Psychological, Fear, Female, Male, Mice, Inbred C57BL, Neural Pathways, Neurons, Synapses, Prefrontal Cortex, CA1 Region, Hippocampal, Basolateral Nuclear Complex
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