title: Re-evaluation of learned information in Drosophila.
abstract: Animals constantly assess the reliability of learned information to optimize their behaviour. On retrieval, consolidated long-term memory can be neutralized by extinction if the learned prediction was inaccurate. Alternatively, retrieved memory can be maintained, following a period of reconsolidation during which it is labile. Although extinction and reconsolidation provide opportunities to alleviate problematic human memories, we lack a detailed mechanistic understanding of memory updating. Here we identify neural operations underpinning the re-evaluation of memory in Drosophila. Reactivation of reward-reinforced olfactory memory can lead to either extinction or reconsolidation, depending on prediction accuracy. Each process recruits activity in specific parts of the mushroom body output network and distinct subsets of reinforcing dopaminergic neurons. Memory extinction requires output neurons with dendrites in the α and α' lobes of the mushroom body, which drive negatively reinforcing dopaminergic neurons that innervate neighbouring zones. The aversive valence of these new extinction memories neutralizes previously learned odour preference. Memory reconsolidation requires the γ2α'1 mushroom body output neurons. This pathway recruits negatively reinforcing dopaminergic neurons innervating the same compartment and re-engages positively reinforcing dopaminergic neurons to reconsolidate the original reward memory. These data establish that recurrent and hierarchical connectivity between mushroom body output neurons and dopaminergic neurons enables memory re-evaluation driven by reward-prediction error.
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Johannes
authors.initials: J
authors.lastname: Felsenberg
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Barnstedt
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Cognigni
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Suewei
authors.initials: S
authors.lastname: Lin
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Waddell
mesh_terms: D000818:Animals; D003712:Dendrites; D004040:Dietary Carbohydrates; D059290:Dopaminergic Neurons / Q000502:physiology; D004331:Drosophila melanogaster / Q000166:cytology / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005260:Female; D007858:Learning / Q000502:physiology*; D008297:Male; D000069077:Memory Consolidation / Q000502:physiology*; D057567:Memory, Long-Term / Q000502:physiology; D023421:Models, Animal; D024521:Mushroom Bodies / Q000166:cytology / Q000502:physiology; D009812:Odorants / Q000032:analysis; D012054:Reinforcement, Psychology; D012201:Reward; D012903:Smell / Q000502:physiology
chemical_list: D004040:Dietary Carbohydrates