Arsenault John T, Rima Samy, Stemmann Heiko, Vanduffel Wim
Laboratory for Neuro- and Psychophysiology, KU Leuven, 3000 Leuven, Belgium; Athinoula A. Martinos Center for Biomedical Imaging, MGH, Charlestown, MA 02129, USA.
Laboratory for Neuro- and Psychophysiology, KU Leuven, 3000 Leuven, Belgium.
Curr Biol. 2014 Jun 16;24(12):1347-1353. doi: 10.1016/j.cub.2014.04.044. Epub 2014 May 29.
Monkey electrophysiology suggests that the activity of the ventral tegmental area (VTA) helps regulate reinforcement learning and motivated behavior, in part by broadcasting prediction error signals throughout the reward system. However, electrophysiological studies do not allow causal inferences regarding the activity of VTA neurons with respect to these processes because they require artificial manipulation of neuronal firing. Rodent studies fulfilled this requirement by demonstrating that electrical and optogenetic VTA stimulation can induce learning and modulate downstream structures. Still, the primate dopamine system has diverged significantly from that of rodents, exhibiting greatly expanded and uniquely distributed cortical and subcortical innervation patterns. Here, we bridge the gap between rodent perturbation studies and monkey electrophysiology using chronic electrical microstimulation of macaque VTA (VTA-EM). VTA-EM was found to reinforce cue selection in an operant task and to motivate future cue selection using a Pavlovian paradigm. Moreover, by combining VTA-EM with concurrent fMRI, we demonstrated that VTA-EM increased fMRI activity throughout most of the dopaminergic reward system. These results establish a causative role for primate VTA in regulating stimulus-specific reinforcement and motivation as well as in modulating activity throughout the reward system.
猴子的电生理学研究表明,腹侧被盖区(VTA)的活动有助于调节强化学习和动机行为,部分原因是通过在整个奖赏系统中传播预测误差信号。然而,电生理学研究无法对VTA神经元活动与这些过程之间进行因果推断,因为它们需要对神经元放电进行人工操控。啮齿动物研究通过证明电刺激和光遗传学刺激VTA可以诱导学习并调节下游结构,满足了这一要求。尽管如此,灵长类动物的多巴胺系统与啮齿动物的多巴胺系统已经有了显著差异,表现出大大扩展且独特分布的皮质和皮质下神经支配模式。在这里,我们使用猕猴VTA的慢性电微刺激(VTA-EM)弥合了啮齿动物扰动研究和猴子电生理学之间的差距。我们发现VTA-EM在操作性任务中强化线索选择,并使用巴甫洛夫范式激发未来的线索选择。此外,通过将VTA-EM与同步功能磁共振成像相结合,我们证明VTA-EM增加了大多数多巴胺能奖赏系统的功能磁共振成像活动。这些结果确立了灵长类动物VTA在调节刺激特异性强化和动机以及调节整个奖赏系统活动方面的因果作用。