RESPONSES OF MONKEY DOPAMINE NEURONS DURING LEARNING OF BEHAVIORAL REACTIONS
RESPONSES OF MONKEY DOPAMINE NEURONS DURING LEARNING OF BEHAVIORAL REACTIONS
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DOI：
10.1152/jn.1992.67.1.145
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发表时间：
1992-01-01
影响因子：
2.5
通讯作者：
SCHULTZ, W
中科院分区：
文献类型：
--
作者：
LJUNGBERG, T;APICELLA, P;SCHULTZ, W
1. 以往的研究表明，多巴胺（DA）神经元对行为意义的刺激，如初级奖励和条件刺激预测奖励和引发行为反应。 本研究探讨了这些反应如何发展和变化时，在不同的学习阶段的刺激的行为意义的变化。 在连续采集两个行为任务的过程中，用可移动微电极记录了两只清醒猴A8、A9和A10区DA神经元的冲动。 DA能神经元的冲动与其他神经元的区别在于其持续时间长（1.8-5.0 ms）和自发频率低（0.5-7.0 imp/s）. 在第一个任务中，动物们学会了在他们面前的一个小盒子里伸手去拿，当它被打开的时候是可见的和可听见的。 在条件反射之前，DA神经元在空盒子打开的最初几次被激活，动物对扫视性眼球运动做出反应。 神经元和行为反应消失的重复刺激呈现。 因此，神经元的反应与一个意想不到的刺激引发定向行为的新奇。 随后，在六次试验中，有一次盒子里放了一小块苹果。 动物对几乎每一个盒子的打开都有眼球扫视的反应，当食物出现时，它们就会伸出手来。 49个神经元中有三分之一在每次开门时被阶段性激活。 当食物存在时，反应更强烈。 因此，DA神经元同时对初级食物奖赏和与奖赏相关的条件刺激作出反应. 每次实验中，当盒子里都有一小块苹果时，动物们都会有规律地做出目标导向的眼睛和手臂运动，76个DA神经元中的大多数都会对开门做出反应。 同样的神经元缺乏对与任务表现无关的光的反应，这些光在交替的会话中在食物盒的位置被照亮，从而证明了刺激的行为意义的特异性。 5. 第二个任务采用了操作性条件反射的反应时间的情况下，动物达到从一个休息的关键向杠杆时，一个小灯被照亮。 DA神经元对非条件光缺乏反应。 在持续2-3天的任务获得过程中，当给予一滴液体奖励以加强到达运动时，25个DA神经元中的一半被阶段性激活。 相比之下，当奖励以固定的间隔（2.5-3.5秒）传递但没有执行任务时，神经元没有被激活。 在既定的任务表现下，神经元失去了对初级奖励的反应，而是被条件光激活。 因此，在学习过程中，对初级奖励的反应被转移到预测奖励的条件刺激上，并有能力引起手臂和眼睛的运动反应。 随后，每只动物都进行了30，000次手臂运动的过度训练。 这导致了自动化的任务性能，缩短了反应和移动时间。 165个神经元对光的反应在反应神经元（46和34%在2个连续阶段中，分别）和总体反应幅度方面进行性降低。 A8和A10区的DA神经元表现出与A9区相似的反应，其中大多数神经元被记录。 特别是，在任何学习阶段，神经元对特定刺激的反应都没有区域偏好。 因此，A8、A9和A10 DA神经元的群体在实验的每个阶段都表现出均匀的反应。 每个神经元要么在每个学习阶段对特定的刺激做出反应，要么对任何刺激都没有反应。 这些数据表明，在收购简单的行为任务，DA神经元响应无条件和条件的突出刺激，吸引动物的注意力，诱导行为激活，并与奖励。 有效的刺激包括：1）新的、意想不到的刺激，引发定向反应; 2）初级奖励，在条件反射期间作为奖励物传递; 3）条件激励刺激，预测奖励并有能力引发行为反应。 过度训练后神经元反应性的降低与注意力和激励过程的减少是平行的，当任务被作为一种习惯执行时，刺激仅仅作为自动任务执行的时间参考。 这些数据提供了进一步的证据，证明DA神经元参与了唤醒、动机和行为激活过程，这些过程决定了行为反应，而无需编码有关行为反应的特定信息。
1. Previous studies have shown that dopamine (DA) neurons respond to stimuli of behavioral significance, such as primary reward and conditioned stimuli predicting reward and eliciting behavioral reactions. The present study investigated how these responses develop and vary when the behavioral significance of stimuli changes during different stages of learning. Impulses from DA neurons were recorded with movable microelectrodes from areas A8, A9, and A10 in two awake monkeys during the successive acquisition of two behavioral tasks. Impulses of DA neurons were distinguished from other neurons by their long duration (1.8-5.0 ms) and low spontaneous frequency (0.5-7.0 imp/s).2. In the first task, animals learned to reach in a small box in front of them when it opened visibly and audibly. Before conditioning, DA neurons were activated the first few times that the empty box opened and animals reacted with saccadic eye movements. Neuronal and behavioral responses disappeared on repeated stimulus presentation. Thus neuronal responses were related to the novelty of an unexpected stimulus eliciting orienting behavior.3. Subsequently, the box contained a small morsel of apple in one out of six trials. Animals reacted with ocular saccades to nearly every box opening and reached out when the morsel was present. One-third of 49 neurons were phasically activated by every door opening. The response was stronger when food was present. Thus DA neurons responded simultaneously to the sight of primary food reward and to the conditioned stimulus associated with reward.4. When the box contained a morsel of apple on every trial, animals regularly reacted with target-directed eye and arm movements, and the majority of 76 DA neurons responded to door opening. The same neurons lacked responses to a light not associated with task performance that was illuminated at the position of the food box in alternate sessions, thus demonstrating specificity for the behavioral significance of stimuli. 5. The second task employed the operant conditioning of a reaction time situation in which animals reached from a resting key toward a lever when a small light was illuminated. DA neurons lacked responses to the unconditioned light. During task acquisition lasting 2-3 days, one-half of 25 DA neurons were phasically activated when a drop of liquid reward was delivered for reinforcing the reaching movement. In contrast, neurons were not activated when reward was delivered at regular intervals (2.5-3.5 s) but a task was not performed.6. With established task performance, neurons lost responses to primary reward and instead were activated in their majority by the conditioned light. Thus the response to primary reward was transferred during learning to the conditioned stimulus that predicted reward and had the capacity to elicit arm and eye movement reactions.7. Subsequently, each animal was overtrained with 30,000 arm movements. This resulted in automated task performance with shortened reaction and movement times. Responses of 165 neurons to the light were progressively reduced in terms of responding neurons (46 and 34% in 2 successive phases, respectively) and overall response magnitude.8. DA neurons in areas A8 and A10 showed responses similar to those in A9, where most neurons were recorded. In particular, there was no regional preference for neurons responding to a particular stimulus during any learning phase. Thus the populations of A8, A9, and A10 DA neurons showed homogeneous responses during each phase of experimentation. Each neuron either responded to a particular stimulus during each learning phase or lacked responses to any stimuli.9. These data suggest that, during acquisition of simple behavioral tasks, DA neurons respond to unconditioned and conditioned salient stimuli that attract the attention of the animal, induce behavioral activation, and are associated with reward. Effective stimuli include 1) novel, unexpected stimuli eliciting orienting reactions; 2) primary reward, when delivered as reinforcer during conditioning; and 3) conditioned incentive stimuli, which predict reward and have the capacity to elicit behavioral reactions. The decreased neuronal responsiveness after overtraining parallels the reduced attentional and incentive processes that occur when the task is performed as a habit and stimuli serve merely as temporal reference for automatic task performance. These data provide further evidence for the involvement of DA neurons in arousing, motivational, and behavioral activating processes that determine behavioral reactivity without encoding specific information about the behavioral reaction.