Janelia Research Campus, HHMI, Ashburn, VA 20147.
Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 2023 Sep 26;120(39):e2221415120. doi: 10.1073/pnas.2221415120. Epub 2023 Sep 21.
Foraging animals must use decision-making strategies that dynamically adapt to the changing availability of rewards in the environment. A wide diversity of animals do this by distributing their choices in proportion to the rewards received from each option, Herrnstein's operant matching law. Theoretical work suggests an elegant mechanistic explanation for this ubiquitous behavior, as operant matching follows automatically from simple synaptic plasticity rules acting within behaviorally relevant neural circuits. However, no past work has mapped operant matching onto plasticity mechanisms in the brain, leaving the biological relevance of the theory unclear. Here, we discovered operant matching in and showed that it requires synaptic plasticity that acts in the mushroom body and incorporates the expectation of reward. We began by developing a dynamic foraging paradigm to measure choices from individual flies as they learn to associate odor cues with probabilistic rewards. We then built a model of the fly mushroom body to explain each fly's sequential choice behavior using a family of biologically realistic synaptic plasticity rules. As predicted by past theoretical work, we found that synaptic plasticity rules could explain fly matching behavior by incorporating stimulus expectations, reward expectations, or both. However, by optogenetically bypassing the representation of reward expectation, we abolished matching behavior and showed that the plasticity rule must specifically incorporate reward expectations. Altogether, these results reveal the first synapse-level mechanisms of operant matching and provide compelling evidence for the role of reward expectation signals in the fly brain.
觅食动物必须使用决策策略，这些策略要能根据环境中奖励的变化情况做出动态调整。许多动物通过赫恩斯坦操作性匹配定律来实现这一点，该定律将动物的选择分配比例与从每种选择中获得的奖励成正比。理论研究为这种普遍存在的行为提供了一种优雅的机械解释，因为操作性匹配是由在行为相关神经回路中起作用的简单突触可塑性规则自动产生的。然而，过去的研究工作并未将操作性匹配映射到大脑中的可塑性机制上，因此该理论的生物学相关性尚不清楚。在这里，我们在果蝇中发现了操作性匹配，并证明它需要在蘑菇体中起作用的突触可塑性，并且要整合对奖励的期望。我们首先开发了一个动态觅食范式，以测量个体果蝇在将气味线索与概率奖励相关联的过程中的选择情况。然后，我们构建了一个果蝇蘑菇体模型，使用一系列具有生物学现实意义的突触可塑性规则来解释每只果蝇的顺序选择行为。正如过去的理论工作所预测的那样，我们发现，通过整合刺激期望、奖励期望或两者，突触可塑性规则可以解释果蝇的匹配行为。然而，通过光遗传学绕过奖励期望的表示，我们消除了匹配行为，并表明可塑性规则必须具体地整合奖励期望。总之，这些结果揭示了操作性匹配的第一个突触水平机制，并为奖励期望信号在果蝇大脑中的作用提供了有力证据。
