Mesostriatal dopamine in Pavlovian reward rate learning
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Principal Investigator: Eric Garr Organization: JOHNS HOPKINS UNIVERSITY Fiscal Year: 2024 Award: $84,364 Funding agency: National Institute on Drug Abuse 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. Terms: <Association Learning><Associative Learning><Attention><Auditory><Axon><Axon Terminals><Behavior><Behavior Control><Behavioral Manipulation><Belief><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Common Rat Strains><Communication><Corpus Striatum><Corpus striatum structure><Cues><DA Neuron><DNA Recombination><Dependence><Dopamine><Dopamine neuron><Environment><Event><Fiber><Future><Genetic Recombination><Goals><Human><Hydroxytyramine><Image><Intracellular Communication and Signaling><Investigation><Learning><Machine Learning><Measures><Mediating><Mesencephalon><Methods><Mid-brain><Midbrain><Midbrain structure><Modeling><Modern Man><Movement><N-Methyl-D-Aspartate Receptors><N-Methylaspartate Receptors><NMDA Receptor-Ionophore Complex><NMDA Receptors><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Neurosciences><Nucleus Accumbens><Opsin><Pavlovian conditioning><Phase><Photometry><Physiologic><Physiological><Population><Presynaptic Nerve Endings><Presynaptic Terminals><Protocol><Protocols documentation><Psychological reinforcement><Rat><Rats Mammals><Rattus><Receptor Activation><Recombination><Reinforcement><Relapse><Reporting><Research><Rewards><Rod-Opsin><Rodent Model><Role><Signal Transduction><Signal Transduction Systems><Signaling><Spottings><Striate Body><Striatum><Sum><Synapses><Synaptic><Synaptic Boutons><Synaptic Terminals><Synaptic plasticity><Time><Ventral Striatum><Ventral Tegmental Area><Video Recording><Videorecording><abused drug><abused drugs><addiction><addictive disorder><associative conditioning><behavioral control><biological signal transduction><body movement><classical conditioning><cohort><conditioning><dopaminergic neuron><drug abused><drug addiction therapy><drug craving><drug of abuse><drugs abused><drugs of abuse><experience><experiment><experimental research><experimental study><experiments><imaging><insight><machine based learning><neural><neuronal><neurotransmitter release><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><optogenetics><postsynaptic><response><social role><striatal><synapse><theories><ventral tegmentum><video recording system>