title: A causal link between prediction errors, dopamine neurons and learning.
abstract: Situations in which rewards are unexpectedly obtained or withheld represent opportunities for new learning. Often, this learning includes identifying cues that predict reward availability. Unexpected rewards strongly activate midbrain dopamine neurons. This phasic signal is proposed to support learning about antecedent cues by signaling discrepancies between actual and expected outcomes, termed a reward prediction error. However, it is unknown whether dopamine neuron prediction error signaling and cue-reward learning are causally linked. To test this hypothesis, we manipulated dopamine neuron activity in rats in two behavioral procedures, associative blocking and extinction, that illustrate the essential function of prediction errors in learning. We observed that optogenetic activation of dopamine neurons concurrent with reward delivery, mimicking a prediction error, was sufficient to cause long-lasting increases in cue-elicited reward-seeking behavior. Our findings establish a causal role for temporally precise dopamine neuron signaling in cue-reward learning, bridging a critical gap between experimental evidence and influential theoretical frameworks.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California, San Francisco, California, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Steinberg
authors.forename: Ronald
authors.initials: R
authors.lastname: Keiflin
authors.forename: Josiah R
authors.initials: JR
authors.lastname: Boivin
authors.forename: Ilana B
authors.initials: IB
authors.lastname: Witten
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Janak
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D003216:Conditioning, Operant / Q000502:physiology*; D003463:Cues; D059290:Dopaminergic Neurons / Q000502:physiology*; D004558:Electric Stimulation; D030762:Estrous Cycle / Q000235:genetics; D005108:Extinction, Psychological / Q000502:physiology; D005260:Female; D005518:Food Preferences / Q000502:physiology; D007839:Functional Laterality / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D062308:Optogenetics; D011237:Predictive Value of Tests; D051381:Rats; D020318:Rats, Long-Evans; D055647:Rats, Transgenic; D012201:Reward; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology*
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D014446:Tyrosine 3-Monooxygenase