@article {SpringerENEURO.0549-20.2021, author = {Magdalena Springer and Martin Paul Nawrot}, title = {A Mechanistic Model for Reward Prediction and Extinction Learning in the Fruit Fly}, volume = {8}, number = {3}, elocation-id = {ENEURO.0549-20.2021}, year = {2021}, doi = {10.1523/ENEURO.0549-20.2021}, publisher = {Society for Neuroscience}, abstract = {Extinction learning, the ability to update previously learned information by integrating novel contradictory information, is of high clinical relevance for therapeutic approaches to the modulation of maladaptive memories. Insect models have been instrumental in uncovering fundamental processes of memory formation and memory update. Recent experimental results in Drosophila melanogaster suggest that, after the behavioral extinction of a memory, two parallel but opposing memory traces coexist, residing at different sites within the mushroom body (MB). Here, we propose a minimalistic circuit model of the Drosophila MB that supports classical appetitive and aversive conditioning and memory extinction. The model is tailored to the existing anatomic data and involves two circuit motives of central functional importance. It employs plastic synaptic connections between Kenyon cells (KCs) and MB output neurons (MBONs) in separate and mutually inhibiting appetitive and aversive learning pathways. Recurrent modulation of plasticity through projections from MBONs to reinforcement-mediating dopaminergic neurons (DAN) implements a simple reward prediction mechanism. A distinct set of four MBONs encodes odor valence and predicts behavioral model output. Subjecting our model to learning and extinction protocols reproduced experimental results from recent behavioral and imaging studies. Simulating the experimental blocking of synaptic output of individual neurons or neuron groups in the model circuit confirmed experimental results and allowed formulation of testable predictions. In the temporal domain, our model achieves rapid learning with a step-like increase in the encoded odor value after a single pairing of the conditioned stimulus (CS) with a reward or punishment, facilitating single-trial learning.}, URL = {https://www.eneuro.org/content/8/3/ENEURO.0549-20.2021}, eprint = {https://www.eneuro.org/content/8/3/ENEURO.0549-20.2021.full.pdf}, journal = {eNeuro} }