Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan; Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
Neuron. 2018 Dec 19;100(6):1513-1526.e4. doi: 10.1016/j.neuron.2018.10.025. Epub 2018 Nov 8.
Animals need to inhibit inappropriate actions that would lead to unwanted outcomes. Although this ability, called response inhibition, is impaired in neurological/psychiatric disorders with dopaminergic dysfunctions, how dopamine regulates response inhibition remains unclear. Here we investigated neuronal signals of the nigrostriatal dopamine system in monkeys performing a saccadic countermanding task. Subsets of dopamine neurons in the substantia nigra and striatal neurons receiving the dopaminergic input were activated when the monkey was required to cancel a planned saccadic eye movement. These activations were stronger when canceling the eye movements was successful compared with failed and were enhanced in demanding trials. The activated dopamine neurons were distributed mainly in the dorsolateral, but not in the ventromedial, part of the nigra. Furthermore, pharmacological blockade of dopaminergic neurotransmission in the striatum dampened the performance of canceling saccadic eye movements. The present findings indicate that disruption of nigrostriatal dopamine signaling causes impairments in response inhibition.
动物需要抑制可能导致不良后果的不当行为。尽管这种被称为反应抑制的能力在多巴胺能功能障碍的神经/精神疾病中受到损害，但多巴胺如何调节反应抑制仍不清楚。在这里，我们研究了猴子在执行扫视性反抑制任务时黑质纹状体多巴胺系统的神经元信号。当猴子需要取消计划中的扫视眼动时，黑质和纹状体中接收多巴胺输入的神经元的亚群被激活。与失败相比，成功取消眼动时的这些激活更强，并且在要求更高的试验中增强。被激活的多巴胺神经元主要分布在黑质的背外侧，但不在腹内侧。此外，纹状体中多巴胺能神经传递的药理学阻断削弱了扫视性眼动取消的表现。本研究结果表明，黑质纹状体多巴胺信号的中断导致反应抑制受损。
