1月18日,美国物理学家组织网报道,美国科学家绘制出了迄今最完整的大脑神经相互作用以增强从学习到服药等行为的图谱,有望为科学家们治疗成瘾开辟新道路。相关研究发表在1月18日出版的《自然》杂志上。
哈佛大学分子和细胞生物学副教授瑙石哥·乌骐达领导的科研团队,在多年研究名为奖赏预测失误的脑部活动过程中得到了上述结果。此前,科学家们认为,预测失误是学习的关键组成部分,也是巴胺神经元放电以对一个意想不到的“奖赏”做出反应以增强导致这种报偿行为的产物。
但乌骐达和哈佛大学以及贝斯以色列女执事医疗中心的同事在最新研究中却指出,“奖赏”预测失误实际上是两类神经元(一种依靠多巴胺的神经元以及一种使用神经传递素GABA的抑制性神经元)之间复杂相互作用的产物。乌骐达表示:“此前,人们都不知道GABA神经元与奖赏和惩罚循环有何关系。我们的最新研究表明,GABA神经元抑制了多巴胺神经元,它们双管齐下来计算奖赏失误。”
研究多巴胺或GABA神经元面临的挑战在于,这两种细胞会相互混合进入大脑内一个比较小的区域,使研究人员很难确切地知道他们正在观察的是哪种细胞,乌骐达团队最终找到了巧妙的办法解决了这一难题。
科学家们对老鼠的两组神经元(一组用于研究多巴胺神经元;一组用于研究GABA神经元)进行了遗传修改,使得当这些神经元被激光脉冲照射时会放电,一旦研究人员确定他们正在测量正确类型的神经元,他们就使用电极来测量这些神经元是否放电以及什么时候会放电以对期望的以及实际的奖赏做出反应。结果表明,当多巴胺神经元放电发出奖赏预测失误信号时,GABA神经元会发出一个期望的奖赏信号。因此,GABA神经元帮助多巴胺神经元计算奖赏预测失误。
乌骐达表示,这项研究发现非常重要,因为它让我们可以采用全新的角度来理解如何对行为进行强化或者通过正常的脑部功能;或者通过破坏这两类神经元相互作用的方式。乌骐达说:“这是一种新的看待成瘾的方式。基于这一理论,我们能研发出新的治疗成瘾的理论。”(生物谷 Bioon.com)
doi:10.1038/nature10754
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Neuron-type-specific signals for reward and punishment in the ventral tegmental area
Jeremiah Y. Cohen,, Sebastian Haesler,Linh Vong, Bradford B. Lowell & Naoshige Uchida
Dopamine has a central role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (that is, reward prediction error), but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neuron based on responses to odours and outcomes: approximately half of the neurons (type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with reward prediction error coding; the other half of neurons showed persistent activity during the delay between odour and outcome that was modulated positively (type II, 31%) or negatively (type III, 18%) by the value of outcomes. Whereas the activity of type I neurons was sensitive to actual outcomes (that is, when the reward was delivered as expected compared to when it was unexpectedly omitted), the activity of type II and type III neurons was determined predominantly by reward-predicting odours. We ‘tagged’ dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of type I and all GABAergic neurons were of type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate reward prediction error.