TY - JOUR T1 - A mechanistic model for reward prediction and extinction learning in the fruit fly JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0549-20.2021 SP - ENEURO.0549-20.2021 AU - Magdalena Springer AU - Martin Paul Nawrot Y1 - 2021/03/30 UR - http://www.eneuro.org/content/early/2021/03/27/ENEURO.0549-20.2021.abstract N2 - 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. Here we propose a minimalistic circuit model of the Drosophila mushroom body that supports classical appetitive and aversive conditioning and memory extinction. The model is tailored to the existing anatomical data and involves two circuit motives of central functional importance. It employs plastic synaptic connections between Kenyon cells and mushroom body 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 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 with a reward or punishment, facilitating single-trial learning.Significance StatementA stressful experience can lead to a strong fear memory where a negative consequence has been associated with a certain stimulus or event. This can trigger fear whenever the same or similar event occurs. Extinction of such a maladaptive memory through extinction learning can thus be of high therapeutic value. Here we present novel theoretical work on the formation and extinction of memories in the fruit fly that suggests an underlying neural circuit mechanism for reward prediction based on recently reported anatomical, physiological and behavioral data. Our findings propose how the theoretical concept of prediction error coding can be realized in a biologically realistic neuronal circuit motif to enable associative learning, saturation of learning, single-trial memory, and memory extinction. ER -