PROJECT SUMMARY Dopamine (DA) signaling in the ventral striatum has received considerable attention for its role in relapse and drug craving, both in rodent models of addiction and in humans. A popular belief is that dopamine neurons in the ventral tegmental area (VTA) communicate a prediction error to the nucleus accumbens core (NAcc), where the error reports the difference between observed and expected values of cues and rewards. A critical assumption is that prediction errors are based on values, and this idea has been used to explain how drugs of abuse exert their reinforcing effects by hijacking DA-mediated value learning. However, in most studies that measure DA cell activity and neurotransmitter release, value is confounded with another variable critical for learning: mutual information, or the degree to which cues in the environment signal relative changes in reward rate. Therefore, the overall goal of this project is to investigate the extent to which an information-theoretic account of learning can be captured by mesostriatal DA dynamics. Behavioral manipulations will utilize established methods of inducing changes in mutual information between cues and rewards independent of value during Pavlovian conditioning in rats. Experiments proposed in Aim 1 will use fiber photometry to assess whether bulk activity in VTA DA neurons and DA release in the NAcc encode prediction errors based on mutual information, and whether cue-evoked responses in NAcc neurons scales with mutual information. Aim 2 will determine whether conditioned behavior will diminish when degrading mutual information between cues and optogenetic DA stimulation in either VTA cell bodies or VTA axon terminals in the NAcc. Experiments in Aim 3 will assess whether optogenetically inhibiting VTA DA neurons that project to the NAcc during moments of Pavlovian information loss will rescue conditioned behavior from dissipating, and whether stimulating cue- sensitive ensembles of NAcc neurons at the onset of information-degraded cues will also have the same effect.