ArticleCurrent biology : CB2021
A midbrain dynorphin circuit promotes threat generalization.
Article in Current biology : CB, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- BLA kappa opioid receptor inputs to the BNST mediate social stress-induced increases in alcohol drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
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- Generalization of negative memories drives the development of psychological distress-related behaviors.Innovation (Cambridge (Mass.)) · 2026Article
- A neural circuit basis for reward-induced suppression of fear generalization and enhancement of fear extinction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The bed nucleus of the stria terminalis as a neuromodulatory target for refractory epilepsy.Frontiers in network physiology · 2026Review
- Kappa Opioid Receptors Control a Stress-Sensitive Brain Circuit and Drive Cocaine Seeking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- An Alternative Gene Editing Strategy Using a Single AAV Vector.Bio-protocol · 2025Article
- Aversive experiences induce valence plasticity of instructive signals to change future learning rules in mice.Communications biology · 2025Article
- Dynorphin modulates reward-seeking actions through a pallido-amygdala cholinergic circuit.Neuron · 2025Article
- A cell-type-specific circuit of somatostatin neurons in the habenula encodes antidepressant action in male mice.Nature communications · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- A dopamine-dependent mechanism for Reward-induced modification of Fear memories.bioRxiv : the preprint server for biology · 2024Article
- Article
- Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.Neuron · 2024Article
- Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.bioRxiv : the preprint server for biology · 2024Article
- Cell specific single viral vector CRISPR/Cas9 editing and genetically encoded tool delivery in the central and peripheral nervous systems.bioRxiv : the preprint server for biology · 2023Article
- The neurophysiological basis of stress and anxiety - comparing neuronal diversity in the bed nucleus of the stria terminalis (BNST) across species.Frontiers in cellular neuroscience · 2023Review
- Modulation of 5-HT release by dynorphin mediates social deficits during opioid withdrawal.Neuron · 2022Article
- The potassium channel auxiliary subunit Kvβ2 (Journal of neurophysiology · 2022Article
- Article
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7 authors at 2 institutions in 3 countries.
Funding
Abstract
Discrimination between predictive and non-predictive threat stimuli decreases as threat intensity increases. The central mechanisms that mediate the transition from discriminatory to generalized threat responding remain poorly resolved. Here, we identify the stress- and dysphoria-associated kappa opioid receptor (KOR) and its ligand dynorphin (Dyn), acting in the ventral tegmental area (VTA), as a key substrate for regulating threat generalization. We identify several dynorphinergic inputs to the VTA and demonstrate that projections from the bed nucleus of the stria terminalis (BNST) and dorsal raphe nucleus (DRN) both contribute to anxiety-like behavior but differentially affect threat generalization. These data demonstrate that conditioned threat discrimination has an inverted "U" relationship with threat intensity and establish a role for KOR/Dyn signaling in the midbrain for promoting threat generalization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.