Eshel Neir, Touponse Gavin C, Wang Allan R, Osterman Amber K, Shank Amei N, Groome Alexandra M, Taniguchi Lara, Cardozo Pinto Daniel F, Tucciarone Jason, Bentzley Brandon S, Malenka Robert C
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Neuron. 2024 Feb 7;112(3):500-514.e5. doi: 10.1016/j.neuron.2023.10.038. Epub 2023 Nov 27.
Striatal dopamine (DA) release has long been linked to reward processing, but it remains controversial whether DA release reflects costs or benefits and how these signals vary with motivation. Here, we measure DA release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) while independently varying costs and benefits and apply behavioral economic principles to determine a mouse's level of motivation. We reveal that DA release in both structures incorporates both reward magnitude and sunk cost. Surprisingly, motivation was inversely correlated with reward-evoked DA release. Furthermore, optogenetically evoked DA release was also heavily dependent on sunk cost. Our results reconcile previous disparate findings by demonstrating that striatal DA release simultaneously encodes cost, benefit, and motivation but in distinct manners over different timescales. Future work will be necessary to determine whether the reduction in phasic DA release in highly motivated animals is due to changes in tonic DA levels.
长期以来，纹状体多巴胺（DA）释放一直与奖赏处理相关联，但DA释放是反映成本还是收益，以及这些信号如何随动机变化，仍存在争议。在这里，我们在独立改变成本和收益的同时，测量伏隔核（NAc）和背外侧纹状体（DLS）中的DA释放，并应用行为经济学原理来确定小鼠的动机水平。我们发现，这两个结构中的DA释放都包含奖赏大小和沉没成本。令人惊讶的是，动机与奖赏诱发的DA释放呈负相关。此外，光遗传学诱发的DA释放也严重依赖于沉没成本。我们的结果通过证明纹状体DA释放在不同时间尺度上以不同方式同时编码成本、收益和动机，调和了先前不同的研究结果。未来有必要开展工作来确定高动机动物中阶段性DA释放的减少是否归因于紧张性DA水平的变化。
