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RESEARCH PRODUCT
Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes
Sebastian BetzRaffael KalischPascal VogelTorfi SigurdssonSevil DuvarciXimena I Salinas-hernándezsubject
0301 basic medicineMaleMouseExtinction PsychologicalPhotometry0302 clinical medicineFear conditioningBiology (General)extinctionGeneral NeuroscienceQRElectroencephalographyGeneral MedicineFearmusculoskeletal systemhumanitiesVentral tegmental areamedicine.anatomical_structureMedicineAnxietymedicine.symptomdopaminePsychologygeographic locationsmedicine.drugResearch ArticleQH301-705.5ScienceOptogeneticsUnconditioned stimulussafety learningGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesextinction ; fear conditioning ; safety learning ; dopamineDopaminemedicineAvoidance LearningAnimalsLearningddc:610General Immunology and MicrobiologyDopaminergic NeuronsVentral Tegmental AreaExtinction (psychology)social sciencesfear conditioningMice Inbred C57BLOptogeneticsElectrophysiology030104 developmental biologyNeuroscience030217 neurology & neurosurgeryNeurosciencedescription
Extinction of fear responses is critical for adaptive behavior and deficits in this form of safety learning are hallmark of anxiety disorders. However, the neuronal mechanisms that initiate extinction learning are largely unknown. Here we show, using single-unit electrophysiology and cell-type specific fiber photometry, that dopamine neurons in the ventral tegmental area (VTA) are activated by the omission of the aversive unconditioned stimulus (US) during fear extinction. This dopamine signal occurred specifically during the beginning of extinction when the US omission is unexpected, and correlated strongly with extinction learning. Furthermore, temporally-specific optogenetic inhibition or excitation of dopamine neurons at the time of the US omission revealed that this dopamine signal is both necessary for, and sufficient to accelerate, normal fear extinction learning. These results identify a prediction error-like neuronal signal that is necessary to initiate fear extinction and reveal a crucial role of DA neurons in this form of safety learning.
year | journal | country | edition | language |
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2018-11-13 |