The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear
Open accessAbstract
The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons in the IL eliminated vHPC-mediated inhibition. In behaving rats, pharmacogenetic activation of vHPC→IL projections impaired extinction recall, whereas silencing IL projectors diminished fear renewal. Intra-IL infusion of GABA receptor agonists or antagonists, respectively, reproduced these effects. Together, our findings describe a previously unknown circuit mechanism for the contextual control of fear, and indicate that vHPC-mediated inhibition of IL is an essential neural substrate for fear relapse.
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“The relapse of extinguished fear is found to be mediated by a feedforward inhibitory pathway from ventral hippocampus to IL cortex, which involves the recruitment of PV+ interneurons in IL 43.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [43]
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Cites
Independent optical excitation of distinct neural populations
Klapoetke, N. C., Murata, Y., Kim, S. S., Pulver, S. R., Birdsey-Benson, A., Cho, Y. K., Morimoto, T. K., Chuong, A. S., Carpenter, E. J., Tian, Z., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2836 · Cited by 2,344
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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
Context and Behavioral Processes in Extinction: Table 1.
Bouton, M. E. (2004) · Learning & Memory · doi:10.1101/lm.78804 · Cited by 1,808
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
Self-citationPetilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex
The Petilla Interneuron Nomenclature Group (PING) (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2402 · Cited by 1,491
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
Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat
Hoover, W. B., & Vertes, R. P. (2007) · Brain Structure and Function · doi:10.1007/s00429-007-0150-4 · Cited by 1,365
Amygdala, medial prefrontal cortex, and hippocampal function in PTSD
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Chemogenetics revealed: DREADD occupancy and activation via converted clozapine
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Behavioral and neurobiological mechanisms of pavlovian and instrumental extinction learning
Bouton, M. E., Maren, S., & McNally, G. P. (2020) · Physiological Reviews · doi:10.1152/physrev.00016.2020 · Cited by 438
Self-citationPrefrontal 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
“Activity-tagging coupled with optogenetic inhibition suggests that threat conditioning and extinction memories exist in separate populations of neurons within the hippocampus [44], and the hippocampus may influence mPFC activity through feed-forward inhibition mechanisms through parvalbumin interneurons [45].”
BackgroundCircuit organization of the rodent medial prefrontal cortex
Anastasiades, P. G., & Carter, A. G. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.03.006 · Cited by 314
Yan, Z., & Rein, B. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01092-3 · Cited by 300
Distinct hippocampal engrams control extinction and relapse of fear memory
Lacagnina, A. F., Brockway, E. T., Crovetti, C. R., Shue, F., McCarty, M. J., Sattler, K. P., Lim, S. C., Santos, S. L., Denny, C. A., & Drew, M. R. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0361-z · Cited by 311
Metadata
- Authors
- 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., Lynch, J. W., Maren, S., & Sah, P.
- Affiliations
- The University of Queensland (AU)
- Texas A&M University (US)
- The University of Texas at Dallas (US)
- University of Copenhagen (DK)
- Corresponding author
- Maren, Stephen
- Sah, Pankaj
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-02-05
- Volume
- 21
- Issue
- 3
- Pages
- 384-392
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5957529
- OpenAlex
- W2797856206
- Cited by
- 226
- References
- 59
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 20 · 2023: 22 · 2022: 24 · 2021: 34 · 2020: 34 · 2019: 30 · 2018: 24
- FWCI
- 18.17
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-07-09)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (F31MH107113, F31MH112208, R01MH065961)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- fear extinction, fear relapse, ventral hippocampus, infralimbic cortex, medial prefrontal cortex, feedforward inhibition, parvalbumin interneurons, somatostatin interneurons, extinction recall, fear renewal, GABA receptors, optogenetics, pharmacogenetics
- MeSH terms
- Amygdala, Animals, Extinction, Psychological, Fear, Hippocampus, Interneurons, Male, Parvalbumins, Somatostatin, Rats, Wistar, Prefrontal Cortex, Receptors, GABA, Patch-Clamp Techniques, Rats
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