A temporal shift in the circuits mediating retrieval of fear memory
Open accessAbstract
Fear memories allow animals to avoid danger, thereby increasing their chances of survival. Fear memories can be retrieved long after learning, but little is known about how retrieval circuits change with time. Here we show that the dorsal midline thalamus of rats is required for the retrieval of auditory conditioned fear at late (24 hours, 7 days, 28 days), but not early (0.5 hours, 6 hours) time points after learning. Consistent with this, the paraventricular nucleus of the thalamus (PVT), a subregion of the dorsal midline thalamus, showed increased c-Fos expression only at late time points, indicating that the PVT is gradually recruited for fear retrieval. Accordingly, the conditioned tone responses of PVT neurons increased with time after training. The prelimbic (PL) prefrontal cortex, which is necessary for fear retrieval, sends dense projections to the PVT. Retrieval at late time points activated PL neurons projecting to the PVT, and optogenetic silencing of these projections impaired retrieval at late, but not early, time points. In contrast, silencing of PL inputs to the basolateral amygdala impaired retrieval at early, but not late, time points, indicating a time-dependent shift in retrieval circuits. Retrieval at late time points also activated PVT neurons projecting to the central nucleus of the amygdala, and silencing these projections at late, but not early, time points induced a persistent attenuation of fear. Thus, the PVT may act as a crucial thalamic node recruited into cortico-amygdalar networks for retrieval and maintenance of long-term fear memories.
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The paraventricular nucleus of the thalamus plays a crucial role in the encoding of threat memories over time and appears to be necessary in shifting the temporal nature of how the mPFC encodes threat memories.
“The paraventricular nucleus of the thalamus plays a crucial role in the encoding of threat memories over time [54] and appears to be necessary in shifting the temporal nature of how the mPFC encodes threat memories [55].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [55]
The Abstract reports a time-dependent shift in fear-memory retrieval circuits: prelimbic prefrontal projections to PVT are required for retrieval at late, but not early, timepoints. It does not show that PVT causes this shift or changes how the mPFC encodes threat memories; the experiments concern retrieval rather than encoding. The claim’s first clause carries a different citation, so this verdict addresses the clause attributed to this paper. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe study sheds light on a previously unrecognized role of mPFC->PVT projections in naturalistic (unconditioned) social processing in addition to their known function in Pavlovian conditioning and extinction.
“Our study sheds light on a previously unrecognized role of mPFC->PVT projections in naturalistic (unconditioned) social processing in addition to their known function in Pavlovian conditioning and extinction 15–18.”
From A prefrontal–paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in mice (2020) · cites this paper as [17]
Fear memory retrieval more than 24 h after conditioning necessitates prelimbic cortex recruitment of inputs from the paraventricular nucleus of the thalamus to the central lateral amygdala.
“fear memory retrieval more than 24 h after conditioning necessitates prelimbic cortex recruitment of inputs from the paraventricular nucleus of the thalamus to CeL114.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [114]
Direct activation of the BLA by prelimbic cortical inputs mediates freezing responses to conditioned stimulus presentations within 6 h of auditory fear conditioning.
“Direct activation of the BLA by prelimbic cortical inputs mediates freezing responses to CS presentations within 6 h of auditory fear conditioning”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [114]
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- Authors
- Do-Monte, F. H., Quiñones-Laracuente, K., & Quirk, G. J.
- Affiliations
- University of Puerto Rico, Medical Sciences Campus (PR)
- Venue
- Nature
- Published
- 2015-01-19
- Volume
- 519
- Issue
- 7544
- Pages
- 460-463
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4376623
- OpenAlex
- W1972768039
- Cited by
- 491
- References
- 30
- Citations by year
- 2026: 31 · 2025: 43 · 2024: 39 · 2023: 52 · 2022: 45 · 2021: 65 · 2020: 42 · 2019: 35 · 2018: 43 · 2017: 38 · 2016: 27 · 2015: 30 · 2012: 1
- FWCI
- 27.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (5p50mh086400-05)
- National Institute of Mental Health (P-50-MH-086400, K99MH105549, R01MH058883, R37MH058883, R00MH105549)
- National Institute of General Medical Sciences (R25GM061838)
- Division of Biological Infrastructure
- National Institute on Minority Health and Health Disparities (G12MD007600)
- 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
- fear memory retrieval, paraventricular thalamus, prelimbic cortex, amygdala, auditory fear conditioning, Fos expression, synaptic potentiation, interneurons, rats, mice, stress response, cingulate cortex
- MeSH terms
- Amygdala, Animals, Conditioning, Psychological, Fear, Male, Memory, Neural Pathways, Neurons, Thalamus, Time Factors, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Prefrontal Cortex, Rats, Optogenetics
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