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

获得奖励和避免惩罚是强有力的行为目标。恰当地说，进化上保守的过程已经进化到能够预测它们的发生。包括人类在内的许多物种都对这些进行了详细的研究。在昆虫中，蘑菇体在这方面的作用是有充分记录的。相比之下，本项目侧重于较少被承认但同样重要的从奖罚终止中学习的过程。的确，获得奖励的感觉很好（获得），但当奖励终止时感觉很糟糕（失去）。这些经历分别导致了对相关线索的食欲记忆和厌恶记忆。反过来，接受惩罚（痛苦）和终止惩罚（解脱）会产生厌恶和食欲记忆。因此，这种依赖于时间的价反转定义了一个2x2的强化相关记忆矩阵，这对动物和人类都很常见（Gerber et al Curr Op Behav Sci 2019）。本项目特别关注黑腹果蝇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)在支配蘑菇体的单个多巴胺能神经元水平上研究了时间依赖性价反转的组织；Ii)研究时间依赖性价反转的遗传结构，重点研究蘑菇体中多巴胺受体下游的分子级联；Iii)并探索时间依赖的效价反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.