Felsenberg Johannes, Barnstedt Oliver, Cognigni Paola, Lin Suewei, Waddell Scott
Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
Nature. 2017 Apr 13;544(7649):240-244. doi: 10.1038/nature21716. Epub 2017 Apr 5.
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.
动物不断评估所学信息的可靠性以优化其行为。在记忆提取时，如果所学预测不准确，巩固的长期记忆可通过消退而被中和。另外，在一段不稳定的重新巩固期之后，提取的记忆可以得以维持。尽管消退和重新巩固为减轻人类的问题记忆提供了机会，但我们对记忆更新缺乏详细的机制理解。在这里，我们确定了果蝇中记忆重新评估背后的神经操作。奖励强化的嗅觉记忆的重新激活可导致消退或重新巩固，这取决于预测准确性。每个过程都会在蘑菇体输出网络的特定部分以及强化多巴胺能神经元的不同子集中引发活动。记忆消退需要在蘑菇体α和α'叶中有树突的输出神经元，这些神经元驱动支配相邻区域的负强化多巴胺能神经元。这些新的消退记忆的厌恶效价会中和先前学到的气味偏好。记忆重新巩固需要γ2α'1蘑菇体输出神经元。这条通路会募集支配同一隔室的负强化多巴胺能神经元，并重新激活正强化多巴胺能神经元以重新巩固原始奖励记忆。这些数据表明，蘑菇体输出神经元和多巴胺能神经元之间的循环和层级连接能够实现由奖励预测误差驱动的记忆重新评估。
