Schultz W, Apicella P, Ljungberg T
Institut de Physiologie, Université de Fribourg, Switzerland.
J Neurosci. 1993 Mar;13(3):900-13. doi: 10.1523/JNEUROSCI.13-03-00900.1993.
The present investigation had two aims: (1) to study responses of dopamine neurons to stimuli with attentional and motivational significance during several steps of learning a behavioral task, and (2) to study the activity of dopamine neurons during the performance of cognitive tasks known to be impaired after lesions of these neurons. Monkeys that had previously learned a simple reaction time task were trained to perform a spatial delayed response task via two intermediate tasks. During the learning of each new task, a total of 25% of 76 dopamine neurons showed phasic responses to the delivery of primary liquid reward, whereas only 9% of 163 neurons responded to this event once task performance was established. This produced an average population response during but not after learning of each task. Reward responses during learning were significantly more numerous and pronounced in area A10, as compared to areas A8 and A9. Dopamine neurons also showed phasic responses to the two conditioned stimuli. These were the instruction cue, which was the first stimulus in each trial and indicated the target of the upcoming arm movement (58% of 76 neurons during and 44% of 163 neurons after learning), and the trigger stimulus, which was a conditioned incentive stimulus predicting reward and eliciting a saccadic eye movement and an arm reaching movement (38% of neurons during and 40% after learning). None of the dopamine neurons showed sustained activity in the delay between the instruction and trigger stimuli that would resemble the activity of neurons in dopamine terminal areas, such as the striatum and frontal cortex. Thus, dopamine neurons respond phasically to alerting external stimuli with behavioral significance whose detection is crucial for learning and performing delayed response tasks. The lack of sustained activity suggests that dopamine neurons do not encode representational processes, such as working memory, expectation of external stimuli or reward, or preparation of movement. Rather, dopamine neurons are involved with transient changes of impulse activity in basic attentional and motivational processes underlying learning and cognitive behavior.
（1）在学习行为任务的几个阶段，研究多巴胺能神经元对具有注意力和动机意义的刺激的反应；（2）在执行已知在这些神经元受损后会受到影响的认知任务期间，研究多巴胺能神经元的活动。先前学会简单反应时任务的猴子，通过两个中间任务被训练来执行空间延迟反应任务。在学习每个新任务的过程中，76个多巴胺能神经元中有25%对给予初级液体奖励表现出相位反应，而一旦任务表现确立，163个神经元中只有9%对该事件有反应。这在每个任务学习期间而非学习后产生了平均群体反应。与A8区和A9区相比，学习期间A10区的奖励反应数量明显更多且更显著。多巴胺能神经元对两种条件刺激也表现出相位反应。这两种刺激分别是指令线索，它是每次试验中的第一个刺激，指示即将到来的手臂运动的目标（学习期间76个神经元中的58%，学习后163个神经元中的44%），以及触发刺激，它是一种条件性激励刺激，预测奖励并引发眼球扫视运动和手臂伸展运动（学习期间38%的神经元，学习后40%）。没有多巴胺能神经元在指令和触发刺激之间的延迟期表现出持续活动，而这种持续活动类似于多巴胺终末区域（如纹状体和额叶皮质）中神经元的活动。因此，多巴胺能神经元对具有行为意义的外部警觉刺激做出相位反应，对这些刺激的检测对于学习和执行延迟反应任务至关重要。缺乏持续活动表明，多巴胺能神经元并不编码诸如工作记忆、对外部刺激或奖励的预期或运动准备等表征过程。相反，多巴胺能神经元参与学习和认知行为基础的基本注意力和动机过程中冲动活动的短暂变化。
