A midbrain dynorphin circuit promotes threat generalization
| Autor: | Barbara Juarez, Marta E. Soden, Lizz Fellinger, Larry S. Zweifel, Yong Sang Jo, Avery C. Hunker, Jordan E. Elum |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Dorsal Raphe Nucleus
Receptors Opioid kappa Ventral Tegmental Area Dynorphin Biology Dynorphins κ-opioid receptor General Biochemistry Genetics and Molecular Biology Ventral tegmental area Midbrain Stria terminalis medicine.anatomical_structure Dorsal raphe nucleus nervous system Dopamine Generalization (learning) medicine Septal Nuclei General Agricultural and Biological Sciences Neuroscience medicine.drug |
| Zdroj: | Current Biology. 31:4388-4396.e5 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2021.07.047 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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