The paraventricular thalamus controls a central amygdala fear circuit
Open accessAbstract
Appropriate responses to an imminent threat brace us for adversities. The ability to sense and predict threatening or stressful events is essential for such adaptive behaviour. In the mammalian brain, one putative stress sensor is the paraventricular nucleus of the thalamus (PVT), an area that is readily activated by both physical and psychological stressors. However, the role of the PVT in the establishment of adaptive behavioural responses remains unclear. Here we show in mice that the PVT regulates fear processing in the lateral division of the central amygdala (CeL), a structure that orchestrates fear learning and expression. Selective inactivation of CeL-projecting PVT neurons prevented fear conditioning, an effect that can be accounted for by an impairment in fear-conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM(+)) CeL neurons, which has previously been shown to store fear memory. Consistently, we found that PVT neurons preferentially innervate SOM(+) neurons in the CeL, and stimulation of PVT afferents facilitated SOM(+) neuron activity and promoted intra-CeL inhibition, two processes that are critical for fear learning and expression. Notably, PVT modulation of SOM(+) CeL neurons was mediated by activation of the brain-derived neurotrophic factor (BDNF) receptor tropomysin-related kinase B (TrkB). As a result, selective deletion of either Bdnf in the PVT or Trkb in SOM(+) CeL neurons impaired fear conditioning, while infusion of BDNF into the CeL enhanced fear learning and elicited unconditioned fear responses. Our results demonstrate that the PVT-CeL pathway constitutes a novel circuit essential for both the establishment of fear memory and the expression of fear responses, and uncover mechanisms linking stress detection in PVT with the emergence of adaptive behaviour.
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These ROIs have been previously associated with fear memory and align with work at the circuit level.
“These ROIs have been previously associated with fear memory56,59-66 and align with work at the circuit level62.”
From Magnetic resonance microscopy maps widespread effects of Alzheimer’s disease on brain structures and behavior in mice (2026) · cites this paper as [61]
The 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 [18]
Activation of somatostatin-positive CeL neurons by the lateral amygdala and paraventricular nucleus of the thalamus drives fear learning through an overall increase in inhibition in the CeL.
“Activation of somatostatin (SOM)-positive CeL neurons by the lateral amygdala75 and paraventricular nucleus of the thalamus76,77 has also been shown to drive fear learning through an overall increase in inhibition in the CeL.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [77]
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- Authors
- Penzo, M. A., Robert, V., Tucciarone, J., De Bundel, D., Wang, M., Van Aelst, L., Darvas, M., Parada, L. F., Palmiter, R. D., He, M., Huang, Z. J., & Li, B.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- University of Washington (US)
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Fudan University (CN)
- Corresponding author
- Penzo, Mario A.
- Li, Bo
- ORCID
- Venue
- Nature
- Published
- 2015-01-19
- Volume
- 519
- Issue
- 7544
- Pages
- 455-459
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4376633
- OpenAlex
- W1968714114
- Cited by
- 506
- References
- 26
- Citations by year
- 2026: 26 · 2025: 33 · 2024: 44 · 2023: 50 · 2022: 58 · 2021: 67 · 2020: 54 · 2019: 47 · 2018: 45 · 2017: 32 · 2016: 24 · 2015: 25
- FWCI
- 25.27
- 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)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (R01MH094705, R01MH082808, R01MH101214)
- National Institute of Neurological Disorders and Stroke (P50NS062684, R01NS082266)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- paraventricular thalamus, central amygdala, fear conditioning, fear memory retrieval, somatostatin interneurons, synaptic potentiation, stress response, prelimbic cortex, fear extinction, fear extinction memory, memory consolidation
- MeSH terms
- Animals, Conditioning, Psychological, Fear, Female, Male, Memory, Neural Pathways, Neuronal Plasticity, Neurons, Somatostatin, Thalamus, Time Factors, Brain-Derived Neurotrophic Factor, Receptor, trkB, Mice, Central Amygdaloid Nucleus
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