Fraser Kurt M, Collins Val, Wolff Amy R, Ottenheimer David J, Bornhoft Kaisa N, Pat Fiona, Chen Bridget J, Janak Patricia H, Saunders Benjamin T
Department of Psychological & Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Curr Biol. 2025 Feb 24;35(4):746-760.e5. doi: 10.1016/j.cub.2024.12.031. Epub 2025 Jan 23.
Adaptive behavior in a dynamic environmental context often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical component of theories of dopamine's function in learning, motivation, and motor control. Yet, how dopamine neurons are involved in the revaluation of cues when the world changes, to alter our behavior, remains unclear. Here, we make use of a complementary set of in vivo approaches to clarify the contributions of the mesolimbic dopamine system to the dynamic reorganization of reward- seeking behavior. Male and female rats were trained to discriminate when a conditioned stimulus would be followed by a sucrose reward by exploiting the prior, non-overlapping presentation of a another discrete cue-an occasion setter. Only when the occasion setter's presentation preceded the conditioned stimulus did the conditioned stimulus predict sucrose delivery, dissociating the average value of the conditioned stimulus from its immediate value, on a trial-to-trial basis. Activity of ventral tegmental area dopamine neurons was essential for rats to successfully update behavioral response to the occasion setter. Moreover, dopamine release in the nucleus accumbens following the conditioned stimulus only occurred when the occasion setter indicated it would predict reward and did not reflect its average expected value. Downstream of dopamine release, we found that neurons in the nucleus accumbens dynamically tracked the value of the conditioned stimulus. Together, these results help refine notions of dopamine function, revealing a prominent contribution of the mesolimbic dopamine system to the rapid revaluation of motivation.
在动态环境中，适应性行为通常需要对偏离已充分学习关联的刺激进行快速重新评估。稳定的价值编码与适当的行为输出之间的差异，仍然是多巴胺在学习、动机和运动控制中功能理论的关键组成部分。然而，当环境变化时，多巴胺神经元如何参与线索的重新评估以改变我们的行为，仍不清楚。在此，我们利用一套互补的体内方法，来阐明中脑边缘多巴胺系统对寻求奖励行为动态重组的贡献。雄性和雌性大鼠接受训练，通过利用另一个离散线索（一个情境设定者）先前的、不重叠的呈现，来辨别条件刺激之后是否会有蔗糖奖励。只有当情境设定者的呈现先于条件刺激时，条件刺激才预示蔗糖的递送，从而在逐次试验的基础上，将条件刺激的平均价值与其即时价值区分开来。腹侧被盖区多巴胺神经元的活动，对于大鼠成功更新对情境设定者的行为反应至关重要。此外，条件刺激后伏隔核中的多巴胺释放，仅在情境设定者表明它会预示奖励时才会发生，而不反映其平均预期价值。在多巴胺释放的下游，我们发现伏隔核中的神经元动态跟踪条件刺激的价值。这些结果共同有助于完善多巴胺功能的概念，揭示中脑边缘多巴胺系统对动机快速重新评估的突出贡献。
