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Publication : Dopamine Neurons Reflect the Uncertainty in Fear Generalization.

First Author  Jo YS Year  2018
Journal  Neuron Volume  100
Issue  4 Pages  916-925.e3
PubMed ID  30318411 Mgi Jnum  J:268055
Mgi Id  MGI:6269225 Doi  10.1016/j.neuron.2018.09.028
Citation  Jo YS, et al. (2018) Dopamine Neurons Reflect the Uncertainty in Fear Generalization. Neuron 100(4):916-925.e3
abstractText  Generalized fear is a maladaptive behavior in which non-threatening stimuli elicit a fearful response. Here, we demonstrate that discrimination between predictive and non-predictive threat stimuli is highly sensitive to probabilistic discounting and increasing threat intensity in mice. We find that dopamine neurons of the ventral tegmental area (VTA) encode both the negative valence of threat-predictive cues and the certainty of threat prediction. As fear generalization emerges, the dopamine neurons that are activated by a threat predictive cue (CS(+)) decrease the amplitude of activation and an equivalent signal emerges to a non-predictive cue (CS(-)). Temporally precise enhancement of dopamine neurons during threat conditioning to high threat levels or uncertain threats can prevent generalization. Moreover, phasic enhancement of genetically captured dopamine neurons activated by threat cues can reverse fear generalization. These findings demonstrate the dopamine neurons reflect the certainty of threat prediction that can be used to inform and update the fear engram.
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