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Dorsal tegmental dopamine neurons gate associative learning of fear
Open accessAbstract
Functional neuroanatomy of Pavlovian fear has identified neuronal circuits and synapses associating conditioned stimuli with aversive events. Hebbian plasticity within these networks requires additional reinforcement to store particularly salient experiences into long-term memory. Here we have identified a circuit that reciprocally connects the ventral periaqueductal gray and dorsal raphe region with the central amygdala and that gates fear learning. We found that ventral periaqueductal gray and dorsal raphe dopaminergic (vPdRD) neurons encode a positive prediction error in response to unpredicted shocks and may reshape intra-amygdala connectivity via a dopamine-dependent form of long-term potentiation. Negative feedback from the central amygdala to vPdRD neurons might limit reinforcement to events that have not been predicted. These findings add a new module to the midbrain dopaminergic circuit architecture underlying associative reinforcement learning and identify vPdRD neurons as a critical component of Pavlovian fear conditioning. We propose that dysregulation of vPdRD neuronal activity may contribute to fear-related psychiatric disorders.
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“It was also recently reported that optogenetic or chemogenetic inhibition of DRN dopamine neurons during fear conditioning suppressed freezing in response to a footshock-predictive cue, suggesting an additional role in aversive responding115.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [115]
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“…to unexpected sensory events and processing aversive experiences [ 12–14 ], however, only a few studies have explored this question for dopaminergic neurons outside the ventral tegmental area (VTA) [ 15 ], and none have specifically addressed their role in risk assessment and defensive behavior.”
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Desmaison, J. D. U., Léna, C., & Popa, D. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.17.759883
Metadata
- Authors
- Groessl, F., Munsch, T., Meis, S., Griessner, J., Kaczanowska, J., Pliota, P., Kargl, D., Badurek, S., Kraitsy, K., Rassoulpour, A., Zuber, J., Lessmann, V., & Haubensak, W.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Center for Behavioral Brain Sciences (DE)
- Vienna BioCenter Core Facilities (AT)
- Charles River Laboratories (United States) (US)
- Corresponding author
- Haubensak, Wulf
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-06-27
- Volume
- 21
- Issue
- 7
- Pages
- 952-962
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6166775
- OpenAlex
- W2811303733
- Cited by
- 118
- References
- 61
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 10 · 2023: 16 · 2022: 9 · 2021: 18 · 2020: 23 · 2019: 16 · 2018: 5
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fear conditioning, ventral periaqueductal gray, dorsal raphe nucleus, central amygdala, long-term potentiation, associative learning, Hebbian plasticity, fear memory
- MeSH terms
- Animals, Association Learning, Behavior, Animal, Conditioning, Classical, Fear, Male, Neural Pathways, Periaqueductal Gray, Tegmentum Mesencephali, Long-Term Potentiation, Mice, Dopaminergic Neurons
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