Tsai Hsing-Chen, Zhang Feng, Adamantidis Antoine, Stuber Garret D, Bonci Antonello, de Lecea Luis, Deisseroth Karl
Neuroscience Program, W080 Clark Center, 318 Campus Drive West, Stanford University, Stanford, CA 94305, USA.
Science. 2009 May 22;324(5930):1080-4. doi: 10.1126/science.1168878. Epub 2009 Apr 23.
Natural rewards and drugs of abuse can alter dopamine signaling, and ventral tegmental area (VTA) dopaminergic neurons are known to fire action potentials tonically or phasically under different behavioral conditions. However, without technology to control specific neurons with appropriate temporal precision in freely behaving mammals, the causal role of these action potential patterns in driving behavioral changes has been unclear. We used optogenetic tools to selectively stimulate VTA dopaminergic neuron action potential firing in freely behaving mammals. We found that phasic activation of these neurons was sufficient to drive behavioral conditioning and elicited dopamine transients with magnitudes not achieved by longer, lower-frequency spiking. These results demonstrate that phasic dopaminergic activity is sufficient to mediate mammalian behavioral conditioning.
自然奖赏和成瘾性药物能够改变多巴胺信号传导,并且已知腹侧被盖区(VTA)的多巴胺能神经元在不同行为条件下会以紧张性或爆发性方式发放动作电位。然而,在自由活动的哺乳动物中,如果没有能够以适当的时间精度控制特定神经元的技术,这些动作电位模式在驱动行为变化中的因果作用一直不清楚。我们使用光遗传学工具在自由活动的哺乳动物中选择性地刺激VTA多巴胺能神经元的动作电位发放。我们发现,这些神经元的爆发性激活足以驱动行为条件反射,并引发多巴胺瞬变,其幅度是通过更长时间、更低频率的放电无法实现的。这些结果表明,爆发性多巴胺能活动足以介导哺乳动物的行为条件反射。