Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties

Environmental cues, through Pavlovian learning, become conditioned stimuli that guide animals towards the acquisition of “rewards” (i.e., food) that are necessary for survival. Here, we test the fundamental role of midbrain dopamine neurons in conferring predictive and motivational properties to cues, independent of external rewards. We demonstrate that brief phasic optogenetic excitation of dopamine neurons, when presented in temporal association with discrete sensory cues, is sufficient to instantiate those cues as conditioned stimuli that subsequently both evoke dopamine neuron activity on their own, and elicit cue-locked conditioned behavior. Critically, we identify highly parcellated functions for dopamine neuron subpopulations projecting to different regions of striatum, revealing dissociable dopamine systems for the generation of incentive value and conditioned movement invigoration. These results show that dopamine neurons orchestrate Pavlovian conditioning via functionally heterogeneous, circuit-specific motivational signals to create, gate, and shape cue-controlled behaviors.