Environmental cues, through Pavlovian learning, become conditioned stimuli that guide animals toward the acquisition of rewards (for example, food) that are necessary for survival. We tested the fundamental role of midbrain dopamine neurons in conferring predictive and motivational properties to cues, independent of external rewards. We found that brief phasic optogenetic excitation of dopamine neurons, when presented in temporal association with discrete sensory cues, was sufficient to instantiate those cues as conditioned stimuli that subsequently both evoked dopamine neuron activity on their own and elicited cue-locked conditioned behavior. Notably, we identified 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. Our results indicate that dopamine neurons orchestrate Pavlovian conditioning via functionally heterogeneous, circuit-specific motivational signals to create, gate, and shape cue-controlled behaviors.
Bibliographical noteFunding Information:
We thank R. Keiflin and all members of the Janak laboratory for discussion and comments on the manuscript; A. Haimbaugh, D. Acs, H. Pribut, K. Lineback, N. Pettas, B. Persaud, and L. Kinny for assistance with histology and behavioral video scoring; P. Fong for conducting surgical procedures for ex vivo physiology studies; K. Deisseroth (Stanford) for the ChR2 construct; E. Boyden (MIT) for the ChrimsonR construct; and the Janelia Research Campus GENIE Project and Stanford Gene Vector and Virus Core for the GCaMP6f construct. This work was supported by National Institutes of Health grants DA036996 (B.T.S.), DA042895 (B.T.S.), AA022290 (J.M.R.), AA025384 (J.M.R.), DA030529 (E.B.M.), and DA035943 (P.H.J.), as well as grants from the Brain and Behavior Research Foundation (B.T.S. and J.M.R.).
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