Matsumoto Masayuki, Hikosaka Okihide
Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-4435, USA.
Nature. 2007 Jun 28;447(7148):1111-5. doi: 10.1038/nature05860. Epub 2007 May 23.
Midbrain dopamine neurons are key components of the brain's reward system, which is thought to guide reward-seeking behaviours. Although recent studies have shown how dopamine neurons respond to rewards and sensory stimuli predicting reward, it is unclear which parts of the brain provide dopamine neurons with signals necessary for these actions. Here we show that the primate lateral habenula, part of the structure called the epithalamus, is a major candidate for a source of negative reward-related signals in dopamine neurons. We recorded the activity of habenula neurons and dopamine neurons while rhesus monkeys were performing a visually guided saccade task with positionally biased reward outcomes. Many habenula neurons were excited by a no-reward-predicting target and inhibited by a reward-predicting target. In contrast, dopamine neurons were excited and inhibited by reward-predicting and no-reward-predicting targets, respectively. Each time the rewarded and unrewarded positions were reversed, both habenula and dopamine neurons reversed their responses as the bias in saccade latency reversed. In unrewarded trials, the excitation of habenula neurons started earlier than the inhibition of dopamine neurons. Furthermore, weak electrical stimulation of the lateral habenula elicited strong inhibitions in dopamine neurons. These results suggest that the inhibitory input from the lateral habenula plays an important role in determining the reward-related activity of dopamine neurons.
中脑多巴胺神经元是大脑奖赏系统的关键组成部分，该系统被认为可引导寻求奖赏的行为。尽管最近的研究已经表明多巴胺神经元如何对奖赏以及预测奖赏的感觉刺激做出反应，但尚不清楚大脑的哪些部分为多巴胺神经元提供这些行为所需的信号。在这里，我们表明，灵长类动物的外侧缰核是上丘脑结构的一部分，是多巴胺神经元中与负性奖赏相关信号来源的主要候选部位。我们在恒河猴执行具有位置偏向性奖赏结果的视觉引导扫视任务时，记录了缰核神经元和多巴胺神经元的活动。许多缰核神经元被预测无奖赏的目标所兴奋，而被预测有奖赏的目标所抑制。相反，多巴胺神经元分别被预测有奖赏和无奖赏的目标所兴奋和抑制。每次奖赏和无奖赏位置反转时，随着扫视潜伏期的偏向反转，缰核和多巴胺神经元都会反转它们的反应。在无奖赏试验中，缰核神经元的兴奋比多巴胺神经元的抑制开始得更早。此外，对外侧缰核的弱电刺激会引起多巴胺神经元的强烈抑制。这些结果表明，来自外侧缰核的抑制性输入在决定多巴胺神经元的奖赏相关活动中起重要作用。
