Timing-dependent valence reversal: DANs, shock, and beyond

获得奖励和避免惩罚是行为的强大目标。相应地，进化上保守的过程已经进化到学习它们发生的预测因子。在许多物种中，包括人类，都有详细的研究。在昆虫中，蘑菇体在这方面的作用是有据可查的。相比之下，本项目的重点是从奖励和惩罚终止中学习的过程，这一过程很少被承认，但同样重要。“善”是善的，“恶”是恶的，“善”是恶的，“恶”是恶的。这些经历分别导致了对相关线索的食欲和厌恶记忆。反过来，接受惩罚（痛苦）与其终止（解脱）导致厌恶和食欲记忆。因此，这种时间依赖性的价反转定义了动物和人类共同的与记忆相关的2x2矩阵（Gerber et al Curr Op Behav Sci 2019）。本项目特别关注黑腹果蝇中的时间依赖性价反转，这是一个简单的实验系统，具有诱人的分析能力，可以揭示行为神经遗传学的一般原理。我们i）在单个多巴胺能神经元支配的蘑菇体水平上研究了时间依赖性效价逆转的组织; ii）研究了时间依赖性效价逆转的遗传结构，重点是蘑菇体中表达的多巴胺受体下游的分子级联; iii）并探索了时间依赖性效价逆转在高阶学习形式中的作用。

Obtaining rewards and avoiding punishment are powerful goals of behavior. Fittingly, evolutionarily conserved processes have evolved to learn predictors of their occurrence. These are studied in detail in many species, including humans. In insects, the role of the mushroom body is well documented in this respect. In contrast, the present project focuses on the much less acknowledged but equally important process of learning from reward and punishment termination. Indeed, it feels good to receive a reward (Gain) but it feels bad when the reward terminates (Loss). These experiences result in appetitive and aversive memory, respectively, of associated cues. In turn, receiving punishment (Pain) versus its termination (Relief) result in aversive and appetitive memory. Such timing-dependent valence reversal thus defines a 2x2 matrix of reinforcement-related memories that is common to animals and humans alike (Gerber et al Curr Op Behav Sci 2019).The present project specifically focuses timing-dependent valence reversal in Drosophila melanogaster, a simple experimental system with enticing analytical power to reveal general principles in behavioral neurogenetics. We i) study the organization of timing-dependent valence reversal at the level of single dopaminergic neurons innervating the mushroom body; ii) investigate the genetic architecture of timing-dependent valence reversal with an emphasis of the molecular cascades downstream of dopamine receptors expressed in the mushroom body; iii) and explore the role of timing-dependent valence reversal in higher-order forms of learning.